Trial Outcomes & Findings for Long-Term Safety and Antibody Persistence of TDV and the Impact of a Booster Dose (NCT NCT03999996)

NCT ID: NCT03999996

Last Updated: 2025-06-12

Results Overview

GMTs of neutralizing antibodies were measured by microneutralization test 50% (MNT50) for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 365 participants
• Primary outcome timeframe: Month 0 (Day 1)
• Results posted on: 2025-06-12

Participant Flow

Participants took part in the study at multiple investigative sites in United States (US) and Mexico from 12 November 2019 to 25 May 2024.

Healthy participants who received Takeda's Dengue Tetravalent Vaccine (TDV) in two parent trials, DEN-304 [NCT03423173] and DEN-315 [NCT03341637] were enrolled to receive either placebo or TDV.

Participant milestones

Measure	Prior to Booster: DEN-304 Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).	Booster Phase: Placebo Participants received TDV placebo-matching 0.5 milliliters (ml) injection, subcutaneous (SC), once at Visit 3 (Month 15) for participants from parent trial DEN-304 (US) or once at Visit 3 (Month 42) for participants from parent trial DEN-315 (Mexico).	Booster Phase: TDV Participants received TDV 0.5 ml, injection, SC, once at Visit 3 (Month 15) for participants from parent trial DEN-304 (US) or once at Visit 3 (Month 42) for participants from parent trial DEN-315 (Mexico).
Prior to Booster STARTED	246	119	0	0
Prior to Booster COMPLETED	149	84	0	0
Prior to Booster NOT COMPLETED	97	35	0	0
Booster Phase STARTED	0	0	118	115
Booster Phase COMPLETED	0	0	115	110
Booster Phase NOT COMPLETED	0	0	3	5

Reasons for withdrawal

Measure	Prior to Booster: DEN-304 Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).	Booster Phase: Placebo Participants received TDV placebo-matching 0.5 milliliters (ml) injection, subcutaneous (SC), once at Visit 3 (Month 15) for participants from parent trial DEN-304 (US) or once at Visit 3 (Month 42) for participants from parent trial DEN-315 (Mexico).	Booster Phase: TDV Participants received TDV 0.5 ml, injection, SC, once at Visit 3 (Month 15) for participants from parent trial DEN-304 (US) or once at Visit 3 (Month 42) for participants from parent trial DEN-315 (Mexico).
Prior to Booster Adverse Event	2	0	0	0
Prior to Booster Lost to Follow-up	17	22	0	0
Prior to Booster Withdrawal of Consent	51	8	0	0
Prior to Booster Death	0	1	0	0
Prior to Booster Reason Not Specified	27	4	0	0
Booster Phase Lost to Follow-up	0	0	3	3
Booster Phase Withdrawal of Consent	0	0	0	1
Booster Phase Reason Not Specified	0	0	0	1

Baseline Characteristics

Long-Term Safety and Antibody Persistence of TDV and the Impact of a Booster Dose

Baseline characteristics by cohort

Measure	Prior to Booster: DEN-304 n=246 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).	Total n=365 Participants Total of all reporting groups
Age, Continuous	44.4 years STANDARD_DEVIATION 11.03 • n=5 Participants	16.3 years STANDARD_DEVIATION 1.77 • n=7 Participants	35.2 years STANDARD_DEVIATION 16.01 • n=5 Participants
Sex: Female, Male Female	145 Participants n=5 Participants	70 Participants n=7 Participants	215 Participants n=5 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	49 Participants n=7 Participants	150 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	119 Participants n=7 Participants	127 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	238 Participants n=5 Participants	0 Participants n=7 Participants	238 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	35 Participants n=5 Participants	0 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) White	201 Participants n=5 Participants	0 Participants n=7 Participants	201 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	117 Participants n=7 Participants	121 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 0 (Day 1)

Population: Per Protocol Set (PPS) included all participants from the Full Analysis Set (FAS) who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial.

GMTs of neutralizing antibodies were measured by microneutralization test 50% (MNT50) for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=239 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) DENV-3	33.7 titer Interval 28.0 to 40.5	29.5 titer Interval 24.1 to 36.1
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) DENV-4	40.0 titer Interval 33.1 to 48.4	27.1 titer Interval 21.9 to 33.6
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) DENV-1	76.8 titer Interval 62.0 to 95.2	88.6 titer Interval 70.4 to 111.5
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) DENV-2	539.6 titer Interval 460.9 to 631.7	425.6 titer Interval 352.7 to 513.5

PRIMARY outcome

Timeframe: Month 12

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=182 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=48 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) DENV-1	58.4 titer Interval 45.0 to 75.7	96.4 titer Interval 69.9 to 132.7
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) DENV-2	427.3 titer Interval 360.2 to 507.0	276.1 titer Interval 208.3 to 365.9
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) DENV-3	32.8 titer Interval 26.5 to 40.4	25.3 titer Interval 18.5 to 34.7
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) DENV-4	30.0 titer Interval 24.4 to 37.0	22.9 titer Interval 17.6 to 29.8

PRIMARY outcome

Timeframe: Month 15 (DEN-304)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=171 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) DENV-1	121.7 titer Interval 93.3 to 158.7	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) DENV-2	560.2 titer Interval 473.9 to 662.2	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) DENV-3	40.3 titer Interval 32.6 to 49.8	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) DENV-4	34.1 titer Interval 27.3 to 42.6	—

PRIMARY outcome

Timeframe: Month 42 (DEN-315)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 3 at Month 42 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=80 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) DENV-1	106.5 titer Interval 80.8 to 140.4	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) DENV-2	202.9 titer Interval 159.5 to 258.2	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) DENV-3	21.9 titer Interval 16.8 to 28.5	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) DENV-4	11.2 titer Interval 9.1 to 13.6	—

PRIMARY outcome

Timeframe: Month 0 [Day 1)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=239 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus:Positive: DENV-1	122.8 titer Interval 59.5 to 253.2	259.3 titer Interval 135.7 to 495.5
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus:Positive: DENV-2	560.1 titer Interval 314.3 to 998.1	714.1 titer Interval 355.2 to 1435.7
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus:Positive: DENV-3	48.2 titer Interval 26.1 to 88.9	118.7 titer Interval 28.3 to 497.3
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus:Positive: DENV-4	61.5 titer Interval 32.1 to 118.2	112.4 titer Interval 29.6 to 427.5
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus:Negative; DENV-1	71.3 titer Interval 57.2 to 88.9	82.0 titer Interval 64.7 to 103.9
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus:Negative; DENV-2	536.4 titer Interval 456.9 to 629.6	410.0 titer Interval 337.1 to 498.6
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus:Negative; DENV-3	31.8 titer Interval 26.3 to 38.5	26.7 titer Interval 22.1 to 32.2
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus:Negative; DENV-4	37.3 titer Interval 30.7 to 45.4	24.5 titer Interval 19.9 to 30.0

PRIMARY outcome

Timeframe: Month 12

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=182 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=48 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Positive; DENV-1	87.2 titer Interval 37.2 to 204.4	93.5 titer Interval 0.0 to 6220000.0
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Positive; DENV-2	544.5 titer Interval 279.1 to 1062.4	272.6 titer Interval 0.0 to 12600000.0
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Positive; DENV-3	48.6 titer Interval 23.2 to 101.6	34.0 titer Interval 9.99 to 99.9
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Positive; DENV-4	48.0 titer Interval 22.2 to 104.0	21.5 titer Interval 16.0 to 28.9
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Negative; DENV-1	54.8 titer Interval 41.7 to 71.9	96.5 titer Interval 69.3 to 134.2
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Negative; DENV-2	411.1 titer Interval 346.6 to 487.6	276.2 titer Interval 206.7 to 369.0
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Negative; DENV-3	30.8 titer Interval 24.8 to 38.2	25.0 titer Interval 18.0 to 34.7
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Negative; DENV-4	27.8 titer Interval 22.6 to 34.4	23.0 titer Interval 17.5 to 30.2

PRIMARY outcome

Timeframe: Month 15 (DEN-304)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=171 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Positive; DENV-1	214.3 titer Interval 80.6 to 569.9	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Positive; DENV-2	484.5 titer Interval 263.4 to 891.3	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Positive; DENV-3	60.4 titer Interval 29.9 to 122.1	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Positive; DENV-4	47.0 titer Interval 21.7 to 102.1	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Negative; DENV-1	110.9 titer Interval 84.9 to 145.0	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Negative; DENV-2	573.6 titer Interval 483.5 to 680.4	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Negative; DENV-3	37.7 titer Interval 30.3 to 46.9	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Negative; DENV-4	32.4 titer Interval 25.7 to 40.7	—

PRIMARY outcome

Timeframe: Month 42 (DEN-315)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 3 at Month 42 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=80 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus:Positive; DENV-1	320.0 titer Interval 119.6 to 856.4	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus:Positive; DENV-2	436.6 titer Interval 156.3 to 1219.1	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus:Positive; DENV-3	80.4 titer Interval 17.5 to 369.3	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus:Positive; DENV-4	23.3 titer Interval 4.3 to 125.1	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus:Negative; DENV-1	95.8 titer Interval 72.2 to 127.2	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus:Negative; DENV-2	188.6 titer Interval 147.3 to 241.4	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus:Negative; DENV-3	19.3 titer Interval 15.1 to 24.8	—
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus:Negative; DENV-4	10.4 titer Interval 8.8 to 12.4	—

PRIMARY outcome

Timeframe: Month 0 (Day 1)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=239 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) DENV-1	85.8 percentage of participants Interval 80.7 to 89.9	92.4 percentage of participants Interval 86.1 to 96.5
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) DENV-2	98.7 percentage of participants Interval 96.4 to 99.7	99.2 percentage of participants Interval 95.4 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) DENV-3	72.4 percentage of participants Interval 66.3 to 78.0	79.8 percentage of participants Interval 71.5 to 86.6
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) DENV-4	80.8 percentage of participants Interval 75.2 to 85.6	76.5 percentage of participants Interval 67.8 to 83.8

PRIMARY outcome

Timeframe: Month 12

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=182 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=48 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) DENV-1	78.6 percentage of participants Interval 71.9 to 84.3	97.9 percentage of participants Interval 88.9 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) DENV-2	100 percentage of participants Interval 98.0 to 100.0	100 percentage of participants Interval 92.6 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) DENV-3	72.0 percentage of participants Interval 64.9 to 78.4	75.0 percentage of participants Interval 60.4 to 86.4
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) DENV-4	76.4 percentage of participants Interval 69.5 to 82.3	83.3 percentage of participants Interval 69.8 to 92.5

PRIMARY outcome

Timeframe: Month 15 (DEN-304)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity Rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=171 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) DENV-1	94.2 percentage of participants Interval 89.5 to 97.2	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) DENV-2	99.4 percentage of participants Interval 96.8 to 100.0	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) DENV-3	81.9 percentage of participants Interval 75.3 to 87.3	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) DENV-4	76.0 percentage of participants Interval 68.9 to 82.2	—

PRIMARY outcome

Timeframe: Month 42 (DEN-315)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 42 for parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=80 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) DENV-1	96.3 percentage of participants Interval 89.4 to 99.2	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) DENV-2	98.8 percentage of participants Interval 93.2 to 100.0	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) DENV-3	71.3 percentage of participants Interval 60.0 to 80.8	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) DENV-4	55.0 percentage of participants Interval 43.5 to 66.2	—

PRIMARY outcome

Timeframe: Month 0 (Day 1)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=239 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 [Month 0 (Day 1]) Parent Trial Baseline Serostatus:Positive; DENV-1	81.8 percentage of participants Interval 64.5 to 93.0	100 percentage of participants Interval 63.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 [Month 0 (Day 1]) Parent Trial Baseline Serostatus:Positive; DENV-2	97.0 percentage of participants Interval 84.2 to 100.0	100 percentage of participants Interval 63.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 [Month 0 (Day 1]) Parent Trial Baseline Serostatus:Positive; DENV-3	75.8 percentage of participants Interval 57.7 to 88.9	100 percentage of participants Interval 63.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 [Month 0 (Day 1]) Parent Trial Baseline Serostatus:Positive; DENV-4	87.9 percentage of participants Interval 71.8 to 96.6	100 percentage of participants Interval 63.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 [Month 0 (Day 1]) Parent Trial Baseline Serostatus:Negative; DENV-1	86.4 percentage of participants Interval 81.0 to 90.8	91.9 percentage of participants Interval 85.2 to 96.2
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 [Month 0 (Day 1]) Parent Trial Baseline Serostatus:Negative; DENV-2	99.0 percentage of participants Interval 96.5 to 99.9	99.1 percentage of participants Interval 95.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 [Month 0 (Day 1]) Parent Trial Baseline Serostatus:Negative; DENV-3	71.8 percentage of participants Interval 65.2 to 77.9	78.4 percentage of participants Interval 69.6 to 85.6
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 [Month 0 (Day 1]) Parent Trial Baseline Serostatus:Negative; DENV-4	79.6 percentage of participants Interval 73.5 to 84.9	74.8 percentage of participants Interval 65.6 to 82.5

PRIMARY outcome

Timeframe: Month 12

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=182 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=48 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Positive; DENV-1	80.0 percentage of participants Interval 59.3 to 93.2	100 percentage of participants Interval 15.8 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Positive; DENV-2	100 percentage of participants Interval 86.3 to 100.0	100 percentage of participants Interval 15.8 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Positive; DENV-3	76.0 percentage of participants Interval 54.9 to 90.6	100 percentage of participants Interval 15.8 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Positive; DENV-4	80.0 percentage of participants Interval 59.3 to 93.2	100 percentage of participants Interval 15.8 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Negative; DENV-1	78.3 percentage of participants Interval 71.1 to 84.5	97.8 percentage of participants Interval 88.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Negative; DENV-2	100 percentage of participants Interval 97.7 to 100.0	100 percentage of participants Interval 92.3 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Negative; DENV-3	71.3 percentage of participants Interval 63.6 to 78.3	73.9 percentage of participants Interval 58.9 to 85.7
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus:Negative; DENV-4	75.8 percentage of participants Interval 68.3 to 82.3	82.6 percentage of participants Interval 68.6 to 92.2

PRIMARY outcome

Timeframe: Month 15 (DEN-304)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=171 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Positive; DENV-1	87.5 percentage of participants Interval 67.6 to 97.3	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Positive; DENV-2	100 percentage of participants Interval 85.8 to 100.0	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Positive; DENV-3	83.3 percentage of participants Interval 62.6 to 95.3	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Positive: DENV-4	79.2 percentage of participants Interval 57.8 to 92.9	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Negative: DENV-1	95.2 percentage of participants Interval 90.4 to 98.1	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Negative: DENV-2	99.3 percentage of participants Interval 96.3 to 100.0	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Negative: DENV-3	81.6 percentage of participants Interval 74.4 to 87.5	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus:Negative: DENV-4	75.5 percentage of participants Interval 67.7 to 82.2	—

PRIMARY outcome

Timeframe: Month 42 (DEN-315)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 42 for parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=80 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) ((DEN-315) Parent Trial Baseline Serostatus:Positive: DENV-1	100 percentage of participants Interval 59.0 to 100.0	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) ((DEN-315) Parent Trial Baseline Serostatus:Positive: DENV-2	100 percentage of participants Interval 59.0 to 100.0	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) ((DEN-315) Parent Trial Baseline Serostatus:Positive: DENV-3	100 percentage of participants Interval 59.0 to 100.0	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) ((DEN-315) Parent Trial Baseline Serostatus:Positive: DENV-4	57.1 percentage of participants Interval 18.4 to 90.1	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) ((DEN-315) Parent Trial Baseline Serostatus:Negative: DENV-1	95.9 percentage of participants Interval 88.5 to 99.1	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) ((DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-2	98.6 percentage of participants Interval 92.6 to 100.0	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) ((DEN-315) Parent Trial Baseline Serostatus; Negative:DENV-3	68.5 percentage of participants Interval 56.6 to 78.9	—
Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) ((DEN-315) Parent Trial Baseline Serostatus; Negative: DENV-4	54.8 percentage of participants Interval 42.7 to 66.5	—

PRIMARY outcome

Timeframe: Month 0 (Day 1)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 1 at Month 0 for both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=239 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) Bivalent	10.9 percentage of participants Interval 7.2 to 15.5	9.2 percentage of participants Interval 4.7 to 15.9
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) Trivalent	20.5 percentage of participants Interval 15.6 to 26.2	18.5 percentage of participants Interval 12.0 to 26.6
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1]) Tetravalent	61.9 percentage of participants Interval 55.4 to 68.1	67.2 percentage of participants Interval 58.0 to 75.6

PRIMARY outcome

Timeframe: Month 12

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=182 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=48 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) Bivalent	12.6 percentage of participants Interval 8.2 to 18.4	10.4 percentage of participants Interval 3.5 to 22.7
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) Trivalent	21.4 percentage of participants Interval 15.7 to 28.1	22.9 percentage of participants Interval 12.0 to 37.3
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12) Tetravalent	57.1 percentage of participants Interval 49.6 to 64.4	66.7 percentage of participants Interval 51.6 to 79.6

PRIMARY outcome

Timeframe: Month 15 (DEN-304)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=171 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) Bivalent	10.5 percentage of participants Interval 6.4 to 16.1	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) Trivalent	17.0 percentage of participants Interval 11.7 to 23.4	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304) Tetravalent	69.0 percentage of participants Interval 61.5 to 75.8	—

PRIMARY outcome

Timeframe: Month 42 (DEN-315)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 42 for parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=80 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) Bivalent	20.0 percentage of participants Interval 11.9 to 30.4	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) Trivalent	27.5 percentage of participants Interval 18.1 to 38.6	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315) Tetravalent	48.8 percentage of participants Interval 37.4 to 60.2	—

PRIMARY outcome

Timeframe: Month 0 (Day 1)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 1 at Month 0 for both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=239 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus;Positive: Bivalent	9.1 percentage of participants Interval 1.9 to 24.3	0 percentage of participants Interval 0.0 to 36.9
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus;Positive: Trivalent	12.1 percentage of participants Interval 3.4 to 28.2	0 percentage of participants Interval 0.0 to 36.9
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus;Positive: Tetravalent	69.7 percentage of participants Interval 51.3 to 84.4	100 percentage of participants Interval 63.1 to 100.0
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus;Negative: Bivalent	11.2 percentage of participants Interval 7.2 to 16.3	9.9 percentage of participants Interval 5.1 to 17.0
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus;Negative: Trivalent	21.8 percentage of participants Interval 16.4 to 28.1	19.8 percentage of participants Interval 12.9 to 28.5
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1]) Parent Trial Baseline Serostatus;Negative: Tetravalent	60.7 percentage of participants Interval 53.7 to 67.4	64.9 percentage of participants Interval 55.2 to 73.7

PRIMARY outcome

Timeframe: Month 12

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for both parent trials (DEN-304 and DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=182 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=48 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus;Positive:Bivalent	4.0 percentage of participants Interval 0.1 to 20.4	0 percentage of participants Interval 0.0 to 84.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus;Positive:Trivalent	20.0 percentage of participants Interval 6.8 to 40.7	0 percentage of participants Interval 0.0 to 84.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus;Positive:Tetravalent	64.0 percentage of participants Interval 42.5 to 82.0	100 percentage of participants Interval 15.8 to 100.0
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus;Negative:Bivalent	14.0 percentage of participants Interval 9.0 to 20.4	10.9 percentage of participants Interval 3.6 to 23.6
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus;Negative: Trivalent	21.7 percentage of participants Interval 15.5 to 28.9	23.9 percentage of participants Interval 12.6 to 38.8
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12) Parent Trial Baseline Serostatus;Negative: Tetravalent	56.1 percentage of participants Interval 47.9 to 64.0	65.2 percentage of participants Interval 49.8 to 78.6

PRIMARY outcome

Timeframe: Month 15 (DEN-304)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. (DEN-304). All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=171 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus; Positive: Bivalent	8.3 percentage of participants Interval 1.0 to 27.0	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus; Positive: Trivalent	8.3 percentage of participants Interval 1.0 to 27.0	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus; Positive: Tetravalent	75.0 percentage of participants Interval 53.3 to 90.2	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus; Negative: Bivalent	10.9 percentage of participants Interval 6.4 to 17.1	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus; Negative: Trivalent	18.4 percentage of participants Interval 12.5 to 25.6	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus; Negative: Tetravalent	68.0 percentage of participants Interval 59.8 to 75.5	—

PRIMARY outcome

Timeframe: Month 42 (DEN-315)

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 42 for parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=80 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus; Positive: Bivalent	0 percentage of participants Interval 0.0 to 41.0	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus; Positive: Trivalent	42.9 percentage of participants Interval 9.9 to 81.6	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus; Positive: Tetravalent	57.1 percentage of participants Interval 18.4 to 90.1	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus; Negative: Bivalent	21.9 percentage of participants Interval 13.1 to 33.1	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus; Negative: Trivalent	26.0 percentage of participants Interval 16.5 to 37.6	—
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus; Negative: Tetravalent	47.9 percentage of participants Interval 36.1 to 60.0	—

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

Population: Per Protocol Set-Booster (PPS-B) included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=102 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=100 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials DENV-1	116.2 titer Interval 86.6 to 156.0	120.7 titer Interval 86.9 to 167.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials DENV-2	404.0 titer Interval 327.2 to 498.8	361.7 titer Interval 279.7 to 467.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials DENV-3	32.3 titer Interval 24.8 to 41.9	30.1 titer Interval 22.5 to 40.3
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials DENV-4	20.8 titer Interval 16.0 to 27.1	21.4 titer Interval 16.1 to 28.3

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=99 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=97 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials DENV-1	110.8 titer Interval 82.2 to 149.5	1438.3 titer Interval 1104.0 to 1873.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials DENV-2	363.4 titer Interval 291.8 to 452.7	1038.8 titer Interval 833.7 to 1294.4
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials DENV-3	27.7 titer Interval 21.0 to 36.5	446.5 titer Interval 356.8 to 558.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials DENV-4	20.0 titer Interval 15.4 to 26.0	273.5 titer Interval 213.2 to 350.8

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=61 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=61 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) DENV-1	126.4 titer Interval 82.2 to 194.4	130.6 titer Interval 81.9 to 208.4
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) DENV-2	583.9 titer Interval 448.5 to 760.2	596.6 titer Interval 453.4 to 785.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) DENV-3	36.9 titer Interval 26.6 to 51.3	39.5 titer Interval 26.3 to 59.6
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) DENV-4	31.3 titer Interval 21.9 to 44.9	29.9 titer Interval 19.9 to 44.8

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=59 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=60 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) DENV-1	120.1 titer Interval 78.5 to 184.0	1254.3 titer Interval 862.2 to 1824.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) DENV-2	499.2 titer Interval 379.7 to 656.4	1121.4 titer Interval 867.5 to 1449.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) DENV-3	30.6 titer Interval 21.4 to 43.5	389.7 titer Interval 280.8 to 540.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) DENV-4	29.4 titer Interval 20.5 to 42.2	260.9 titer Interval 189.0 to 360.1

PRIMARY outcome

Timeframe: Pre-booster dose at Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=41 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=39 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) DENV-1	102.6 titer Interval 70.6 to 149.0	106.7 titer Interval 68.3 to 166.7
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) DENV-2	233.5 titer Interval 176.1 to 309.8	165.4 titer Interval 110.7 to 247.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) DENV-3	26.4 titer Interval 17.0 to 41.1	19.6 titer Interval 13.6 to 28.2
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) DENV-4	11.3 titer Interval 8.3 to 15.5	12.7 titer Interval 9.4 to 17.1

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=37 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) DENV-1	98.4 titer Interval 65.1 to 148.7	1795.8 titer Interval 1273.5 to 2532.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) DENV-2	227.5 titer Interval 164.5 to 314.6	917.6 titer Interval 607.2 to 1386.7
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) DENV-3	24.0 titer Interval 15.2 to 37.8	556.8 titer Interval 431.6 to 718.3
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) DENV-4	11.3 titer Interval 8.3 to 15.4	295.3 titer Interval 196.0 to 444.8

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=102 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=100 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-1	165.0 titer Interval 62.2 to 437.8	310.4 titer Interval 67.2 to 1434.4
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-2	353.6 titer Interval 192.1 to 650.8	771.3 titer Interval 334.8 to 1776.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-3	53.8 titer Interval 23.4 to 123.6	88.8 titer Interval 25.1 to 313.4
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-4	27.7 titer Interval 14.0 to 55.0	43.5 titer Interval 10.6 to 177.6
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-1	110.4 titer Interval 80.8 to 150.9	106.1 titer Interval 77.2 to 145.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-2	411.9 titer Interval 327.7 to 517.8	326.2 titer Interval 249.4 to 426.7
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-3	30.0 titer Interval 22.7 to 39.6	26.0 titer Interval 19.6 to 34.4
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-4	20.0 titer Interval 15.0 to 26.7	19.4 titer Interval 14.8 to 25.4

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=99 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=97 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-1	170.5 titer Interval 59.7 to 487.0	1192.5 titer Interval 343.2 to 4143.7
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-2	264.2 titer Interval 124.8 to 559.2	1533.3 titer Interval 720.1 to 3264.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-3	46.2 titer Interval 16.9 to 126.4	286.5 titer Interval 124.6 to 658.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-4	34.4 titer Interval 19.6 to 60.5	204.2 titer Interval 83.4 to 500.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-1	104.4 titer Interval 76.2 to 143.2	1473.2 titer Interval 1129.4 to 1921.6
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-2	379.8 titer Interval 301.1 to 479.0	988.3 titer Interval 783.4 to 1246.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-3	25.8 titer Interval 19.4 to 34.4	472.6 titer Interval 374.1 to 597.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-4	18.6 titer Interval 13.9 to 24.8	283.9 titer Interval 218.3 to 369.2

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=61 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=61 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-1	120.5 titer Interval 37.2 to 390.0	368.4 titer Interval 44.6 to 3040.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-2	368.8 titer Interval 175.4 to 775.7	839.4 titer Interval 298.9 to 2357.3
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-3	39.4 titer Interval 19.3 to 80.6	102.1 titer Interval 19.0 to 549.3
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-4	22.9 titer Interval 11.8 to 44.6	59.1 titer Interval 10.3 to 339.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-1	127.6 titer Interval 79.0 to 206.0	109.2 titer Interval 70.2 to 169.7
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-2	639.0 titer Interval 480.4 to 849.9	562.4 titer Interval 423.1 to 747.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-3	36.4 titer Interval 25.0 to 53.2	33.6 titer Interval 22.5 to 50.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-4	33.3 titer Interval 22.0 to 50.5	26.5 titer Interval 17.8 to 39.5

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=59 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=60 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-1	125.6 titer Interval 32.3 to 488.7	1124.7 titer Interval 182.3 to 6939.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-2	264.3 titer Interval 105.0 to 665.2	1545.0 titer Interval 528.1 to 4519.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-3	29.3 titer Interval 11.6 to 74.3	239.1 titer Interval 72.7 to 786.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-4	29.8 titer Interval 19.5 to 45.6	202.8 titer Interval 57.6 to 714.0
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-1	119.2 titer Interval 75.0 to 189.3	1275.5 titer Interval 879.5 to 1849.6
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-2	559.8 titer Interval 422.3 to 742.0	1067.4 titer Interval 820.0 to 1389.6
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-3	30.8 titer Interval 20.7 to 45.8	420.1 titer Interval 297.4 to 593.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-4	29.4 titer Interval 19.2 to 44.8	271.1 titer Interval 193.3 to 380.4

PRIMARY outcome

Timeframe: Pre-booster dose at Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=41 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=39 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-1	470.4 titer Interval 25.4 to 8709.7	185.7 titer Interval 11.7 to 2940.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-2	307.1 titer Interval 19.8 to 4754.2	598.4 titer Interval 15.8 to 22694.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-3	151.1 titer Interval 0.7 to 34960.6	58.2 titer Interval 1.5 to 2257.4
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-4	52.5 titer Interval 0.7 to 3894.5	17.2 titer Interval 0.1 to 3545.3
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-1	91.0 titer Interval 63.1 to 131.1	101.9 titer Interval 63.5 to 163.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-2	228.5 titer Interval 170.5 to 306.3	148.6 titer Interval 99.7 to 221.4
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-3	23.0 titer Interval 15.2 to 34.8	17.9 titer Interval 12.5 to 25.7
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-4	10.0 titer Interval 7.6 to 13.2	12.3 titer Interval 9.4 to 16.2

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=37 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-1	427.0 titer Interval 45.4 to 4020.4	1393.8 titer Interval 219.3 to 8859.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-2	264.1 titer Interval 8.7 to 8032.8	1502.5 titer Interval 236.0 to 9565.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-3	180.8 titer Interval 1.1 to 29718.0	464.2 titer Interval 204.7 to 1052.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-4	53.0 titer Interval 0.9 to 3256.9	208.0 titer Interval 18.4 to 2353.2
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-1	87.3 titer Interval 57.6 to 132.5	1836.5 titer Interval 1269.6 to 2656.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-2	224.8 titer Interval 160.9 to 314.1	878.5 titer Interval 563.9 to 1368.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-3	20.4 titer Interval 13.4 to 31.0	565.8 titer Interval 429.2 to 745.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-4	10.0 titer Interval 7.7 to 13.1	304.5 titer Interval 196.5 to 472.0

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 5, 6 months post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=96 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=92 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials DENV-1	94.2 titer Interval 66.9 to 132.7	464.9 titer Interval 336.1 to 642.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials DENV-2	305.2 titer Interval 244.7 to 380.7	552.5 titer Interval 442.1 to 690.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials DENV-3	27.4 titer Interval 21.4 to 35.3	159.5 titer Interval 122.6 to 207.4
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials DENV-4	16.7 titer Interval 13.0 to 21.5	87.5 titer Interval 65.8 to 116.2

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=56 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=54 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) DENV-1	107.8 titer Interval 65.0 to 179.0	410.9 titer Interval 259.7 to 650.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) DENV-2	433.0 titer Interval 321.4 to 583.5	689.4 titer Interval 530.6 to 895.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) DENV-3	30.7 titer Interval 21.9 to 42.9	133.5 titer Interval 90.5 to 197.0
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) DENV-4	24.3 titer Interval 16.7 to 35.3	89.2 titer Interval 60.5 to 131.7

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=38 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) DENV-1	78.0 titer Interval 50.6 to 120.2	553.9 titer Interval 350.8 to 874.6
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) DENV-2	187.0 titer Interval 142.3 to 245.6	403.4 titer Interval 275.1 to 591.6
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) DENV-3	23.5 titer Interval 15.9 to 34.6	205.2 titer Interval 149.1 to 282.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) DENV-4	9.9 titer Interval 7.8 to 12.5	85.0 titer Interval 55.3 to 130.6

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=96 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=92 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-1	166.2 titer Interval 48.3 to 571.7	435.8 titer Interval 106.8 to 1777.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-2	278.9 titer Interval 108.9 to 714.1	699.2 titer Interval 305.0 to 1603.0
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-3	39.0 titer Interval 18.8 to 80.8	137.1 titer Interval 44.9 to 418.7
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-4	22.0 titer Interval 12.1 to 40.1	83.6 titer Interval 25.0 to 279.0
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-1	88.2 titer Interval 61.5 to 126.5	469.4 titer Interval 338.9 to 650.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-2	308.4 titer Interval 245.1 to 387.9	533.4 titer Interval 422.9 to 672.6
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-3	26.3 titer Interval 20.1 to 34.5	163.1 titer Interval 125.1 to 212.7
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-4	16.2 titer Interval 12.3 to 21.3	88.1 titer Interval 66.1 to 117.3

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=56 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=54 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-1	154.2 titer Interval 30.2 to 786.6	461.7 titer Interval 68.8 to 3098.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-2	337.6 titer Interval 104.5 to 1090.2	825.4 titer Interval 309.0 to 2205.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-3	37.5 titer Interval 14.4 to 98.0	145.5 titer Interval 32.0 to 661.2
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-4	21.7 titer Interval 10.2 to 46.3	95.7 titer Interval 21.6 to 423.2
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-1	101.6 titer Interval 58.6 to 176.2	401.4 titer Interval 254.9 to 632.2
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-2	451.4 titer Interval 330.8 to 615.9	665.0 titer Interval 508.0 to 870.6
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-3	29.7 titer Interval 20.5 to 43.0	131.3 titer Interval 88.3 to 195.1
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-4	24.8 titer Interval 16.2 to 37.9	88.0 titer Interval 59.0 to 131.2

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=38 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-1	223.9 titer Interval 31.8 to 1574.3	366.4 titer Interval 8.2 to 16297.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-2	129.9 titer Interval 0.8 to 21199.9	425.0 titer Interval 9.5 to 19098.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-3	45.5 titer Interval 6.5 to 319.1	114.5 titer Interval 6.0 to 2196.9
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-4	23.2 titer Interval 0.0 to 23073.9	55.8 titer Interval 0.3 to 10826.4
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-1	73.8 titer Interval 47.1 to 115.6	573.9 titer Interval 355.3 to 927.0
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-2	190.6 titer Interval 143.4 to 253.4	401.6 titer Interval 269.9 to 597.6
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-3	22.7 titer Interval 15.1 to 34.0	215.7 titer Interval 155.4 to 299.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-4	9.4 titer Interval 7.5 to 11.9	88.2 titer Interval 57.3 to 135.7

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=102 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=100 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials DENV-1	98.0 percentage of participants Interval 93.1 to 99.8	94.0 percentage of participants Interval 87.4 to 97.8
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials DENV-2	100 percentage of participants Interval 96.4 to 100.0	99.0 percentage of participants Interval 94.6 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials DENV-3	80.4 percentage of participants Interval 71.4 to 87.6	73.0 percentage of participants Interval 63.2 to 81.4
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials DENV-4	66.7 percentage of participants Interval 56.6 to 75.7	67.0 percentage of participants Interval 56.9 to 76.1

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=99 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=97 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials DENV-1	98.0 percentage of participants Interval 92.9 to 99.8	100 percentage of participants Interval 96.3 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials DENV-2	100 percentage of participants Interval 96.3 to 100.0	100 percentage of participants Interval 96.3 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials DENV-3	71.7 percentage of participants Interval 61.8 to 80.3	100 percentage of participants Interval 96.3 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials DENV-4	66.7 percentage of participants Interval 56.5 to 75.8	100 percentage of participants Interval 96.3 to 100.0

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=61 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=61 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) DENV-1	96.7 percentage of participants Interval 88.7 to 99.6	95.1 percentage of participants Interval 86.3 to 99.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) DENV-2	100 percentage of participants Interval 94.1 to 100.0	100 percentage of participants Interval 94.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) DENV-3	83.6 percentage of participants Interval 71.9 to 91.8	77.0 percentage of participants Interval 64.5 to 86.8
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) DENV-4	75.4 percentage of participants Interval 62.7 to 85.5	72.1 percentage of participants Interval 59.2 to 82.9

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=59 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=60 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) DENV-1	98.3 percentage of participants Interval 90.9 to 100.0	100 percentage of participants Interval 94.0 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) DENV-2	100 percentage of participants Interval 93.9 to 100.0	100 percentage of participants Interval 94.0 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) DENV-3	74.6 percentage of participants Interval 61.6 to 85.0	100 percentage of participants Interval 94.0 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) DENV-4	76.3 percentage of participants Interval 63.4 to 86.4	100 percentage of participants Interval 94.0 to 100.0

PRIMARY outcome

Timeframe: Pre-booster dose at Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=41 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=39 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) DENV-1	100 percentage of participants Interval 91.4 to 100.0	92.3 percentage of participants Interval 79.1 to 98.4
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) DENV-2	100 percentage of participants Interval 91.4 to 100.0	97.4 percentage of participants Interval 86.5 to 99.9
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) DENV-3	75.6 percentage of participants Interval 59.7 to 87.6	66.7 percentage of participants Interval 49.8 to 80.9
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) DENV-4	53.7 percentage of participants Interval 37.4 to 69.3	59.0 percentage of participants Interval 42.1 to 74.4

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=37 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) DENV-1	97.5 percentage of participants Interval 86.8 to 99.9	100 percentage of participants Interval 90.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) DENV-2	100 percentage of participants Interval 91.2 to 100.0	100 percentage of participants Interval 90.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) DENV-3	67.5 percentage of participants Interval 50.9 to 81.4	100 percentage of participants Interval 90.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) DENV-4	52.5 percentage of participants Interval 36.1 to 68.5	100 percentage of participants Interval 90.5 to 100.0

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=102 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=100 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-1	92.3 percentage of participants Interval 64.0 to 99.8	91.7 percentage of participants Interval 61.5 to 99.8
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-2	100 percentage of participants Interval 75.3 to 100.0	100 percentage of participants Interval 73.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-3	92.3 percentage of participants Interval 64.0 to 99.8	83.3 percentage of participants Interval 51.6 to 97.9
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-4	84.6 percentage of participants Interval 54.6 to 98.1	66.7 percentage of participants Interval 34.9 to 90.1
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-1	98.9 percentage of participants Interval 93.9 to 100.0	94.3 percentage of participants Interval 87.2 to 98.1
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-2	100 percentage of participants Interval 95.9 to 100.0	98.9 percentage of participants Interval 93.8 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-3	78.7 percentage of participants Interval 68.7 to 86.6	71.6 percentage of participants Interval 61.0 to 80.7
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-4	64.0 percentage of participants Interval 53.2 to 73.9	67.0 percentage of participants Interval 56.2 to 76.7

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=99 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=97 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-1	91.7 percentage of participants Interval 61.5 to 99.8	100 percentage of participants Interval 71.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-2	100 percentage of participants Interval 73.5 to 100.0	100 percentage of participants Interval 71.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-3	83.3 percentage of participants Interval 51.6 to 97.9	100 percentage of participants Interval 71.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-4	100 percentage of participants Interval 73.5 to 100.0	100 percentage of participants Interval 71.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-1	98.9 percentage of participants Interval 93.8 to 100.0	100 percentage of participants Interval 95.8 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-2	100 percentage of participants Interval 95.8 to 100.0	100 percentage of participants Interval 95.8 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-3	70.1 percentage of participants Interval 59.4 to 79.5	100 percentage of participants Interval 95.8 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-4	62.1 percentage of participants Interval 51.0 to 72.3	100 percentage of participants Interval 95.8 to 100.0

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=61 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=61 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-1	90.0 percentage of participants Interval 55.5 to 99.7	88.9 percentage of participants Interval 51.8 to 99.7
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-2	100 percentage of participants Interval 69.2 to 100.0	100 percentage of participants Interval 66.4 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-3	90.0 percentage of participants Interval 55.5 to 99.7	77.8 percentage of participants Interval 40.0 to 97.2
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-4	80.0 percentage of participants Interval 44.4 to 97.5	77.8 percentage of participants Interval 40.0 to 97.2
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-1	98.0 percentage of participants Interval 89.6 to 100.0	96.2 percentage of participants Interval 86.8 to 99.5
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-2	100 percentage of participants Interval 93.0 to 100.0	100 percentage of participants Interval 93.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-3	82.4 percentage of participants Interval 69.1 to 91.6	76.9 percentage of participants Interval 63.2 to 87.5
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-4	74.5 percentage of participants Interval 60.4 to 85.7	71.2 percentage of participants Interval 56.9 to 82.9

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=59 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=60 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-1	88.9 percentage of participants Interval 51.8 to 99.7	100 percentage of participants Interval 63.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-2	100 percentage of participants Interval 66.4 to 100.0	100 percentage of participants Interval 63.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-3	77.8 percentage of participants Interval 40.0 to 97.2	100 percentage of participants Interval 63.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-4	100 percentage of participants Interval 66.4 to 100.0	100 percentage of participants Interval 63.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-1	100 percentage of participants Interval 92.9 to 100.0	100 percentage of participants Interval 93.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-2	100 percentage of participants Interval 92.9 to 100.0	100 percentage of participants Interval 93.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-3	74.0 percentage of participants Interval 59.7 to 85.4	100 percentage of participants Interval 93.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-4	72.0 percentage of participants Interval 57.5 to 83.8	100 percentage of participants Interval 93.2 to 100.0

PRIMARY outcome

Timeframe: Pre-booster dose at Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=41 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=39 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-1	100 percentage of participants Interval 29.2 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-2	100 percentage of participants Interval 29.2 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-3	100 percentage of participants Interval 29.2 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-4	100 percentage of participants Interval 29.2 to 100.0	33.3 percentage of participants Interval 0.8 to 90.6
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-1	100 percentage of participants Interval 90.7 to 100.0	91.7 percentage of participants Interval 77.5 to 98.2
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-2	100 percentage of participants Interval 90.7 to 100.0	97.2 percentage of participants Interval 85.5 to 99.9
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-3	73.7 percentage of participants Interval 56.9 to 86.6	63.9 percentage of participants Interval 46.2 to 79.2
Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-4	50.0 percentage of participants Interval 33.4 to 66.6	61.1 percentage of participants Interval 43.5 to 76.9

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=37 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-1	100 percentage of participants Interval 29.2 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-2	100 percentage of participants Interval 29.2 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-3	100 percentage of participants Interval 29.2 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-4	100 percentage of participants Interval 29.2 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-1	97.3 percentage of participants Interval 85.8 to 99.9	100 percentage of participants Interval 89.7 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-2	100 percentage of participants Interval 90.5 to 100.0	100 percentage of participants Interval 89.7 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-3	64.9 percentage of participants Interval 47.5 to 79.8	100 percentage of participants Interval 89.7 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-4	48.6 percentage of participants Interval 31.9 to 65.6	100 percentage of participants Interval 89.7 to 100.0

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=96 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=92 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials DENV-1	90.6 percentage of participants Interval 82.9 to 95.6	96.7 percentage of participants Interval 90.8 to 99.3
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials DENV-2	100 percentage of participants Interval 96.2 to 100.0	100 percentage of participants Interval 96.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials DENV-3	76.0 percentage of participants Interval 66.3 to 84.2	98.9 percentage of participants Interval 94.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials DENV-4	63.5 percentage of participants Interval 53.1 to 73.1	94.6 percentage of participants Interval 87.8 to 98.2

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=56 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=54 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) DENV-1	89.3 percentage of participants Interval 78.1 to 96.0	96.3 percentage of participants Interval 87.3 to 99.5
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) DENV-2	100 percentage of participants Interval 93.6 to 100.0	100 percentage of participants Interval 93.4 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) DENV-3	78.6 percentage of participants Interval 65.6 to 88.4	98.1 percentage of participants Interval 90.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) DENV-4	71.4 percentage of participants Interval 57.8 to 82.7	96.3 percentage of participants Interval 87.3 to 99.5

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=38 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) DENV-1	92.5 percentage of participants Interval 79.6 to 98.4	97.4 percentage of participants Interval 86.2 to 99.9
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) DENV-2	100 percentage of participants Interval 91.2 to 100.0	100 percentage of participants Interval 90.7 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) DENV-3	72.5 percentage of participants Interval 56.1 to 85.4	100 percentage of participants Interval 90.7 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) DENV-4	52.5 percentage of participants Interval 36.1 to 68.5	92.1 percentage of participants Interval 78.6 to 98.3

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=96 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=92 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-1	90.0 percentage of participants Interval 55.5 to 99.7	91.7 percentage of participants Interval 61.5 to 99.8
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-2	100 percentage of participants Interval 69.2 to 100.0	100 percentage of participants Interval 73.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-3	90.0 percentage of participants Interval 55.5 to 99.7	91.7 percentage of participants Interval 61.5 to 99.8
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Positive: DENV-4	90.0 percentage of participants Interval 55.5 to 99.7	83.3 percentage of participants Interval 51.6 to 97.9
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-1	90.7 percentage of participants Interval 82.5 to 95.9	97.5 percentage of participants Interval 91.3 to 99.7
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-2	100 percentage of participants Interval 95.8 to 100.0	100 percentage of participants Interval 95.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-3	74.4 percentage of participants Interval 63.9 to 83.2	100 percentage of participants Interval 95.5 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus;Negative: DENV-4	60.5 percentage of participants Interval 49.3 to 70.8	96.3 percentage of participants Interval 89.4 to 99.2

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=56 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=54 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-1	87.5 percentage of participants Interval 47.3 to 99.7	88.9 percentage of participants Interval 51.8 to 99.7
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-2	100 percentage of participants Interval 63.1 to 100.0	100 percentage of participants Interval 66.4 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-3	87.5 percentage of participants Interval 47.3 to 99.7	88.9 percentage of participants Interval 51.8 to 99.7
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Positive: DENV-4	87.5 percentage of participants Interval 47.3 to 99.7	88.9 percentage of participants Interval 51.8 to 99.7
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-1	89.6 percentage of participants Interval 77.3 to 96.5	97.8 percentage of participants Interval 88.2 to 99.9
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-2	100 percentage of participants Interval 92.6 to 100.0	100 percentage of participants Interval 92.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-3	77.1 percentage of participants Interval 62.7 to 88.0	100 percentage of participants Interval 92.1 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus;Negative: DENV-4	68.8 percentage of participants Interval 53.7 to 81.3	97.8 percentage of participants Interval 88.2 to 99.9

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=38 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-1	100 percentage of participants Interval 15.8 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-2	100 percentage of participants Interval 15.8 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-3	100 percentage of participants Interval 15.8 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Positive: DENV-4	100 percentage of participants Interval 15.8 to 100.0	66.7 percentage of participants Interval 9.4 to 99.2
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-1	92.1 percentage of participants Interval 78.6 to 98.3	97.1 percentage of participants Interval 85.1 to 99.9
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-2	100 percentage of participants Interval 90.7 to 100.0	100 percentage of participants Interval 90.0 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-3	71.1 percentage of participants Interval 54.1 to 84.6	100 percentage of participants Interval 90.0 to 100.0
Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus;Negative: DENV-4	50.0 percentage of participants Interval 33.4 to 66.6	94.3 percentage of participants Interval 80.8 to 99.3

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=102 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=100 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials Bivalent	15.7 percentage of participants Interval 9.2 to 24.2	16.0 percentage of participants Interval 9.4 to 24.7
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials Trivalent	20.6 percentage of participants Interval 13.2 to 29.7	20.0 percentage of participants Interval 12.7 to 29.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials Tetravalent	62.7 percentage of participants Interval 52.6 to 72.1	59.0 percentage of participants Interval 48.7 to 68.7

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=99 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=97 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials Bivalent	18.2 percentage of participants Interval 11.1 to 27.2	0 percentage of participants Interval 0.0 to 3.7
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials Trivalent	24.2 percentage of participants Interval 16.2 to 33.9	0 percentage of participants Interval 0.0 to 3.7
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials Tetravalent	56.6 percentage of participants Interval 46.2 to 66.5	100 percentage of participants Interval 96.3 to 100.0

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=61 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=61 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) Bivalent	11.5 percentage of participants Interval 4.7 to 22.2	14.8 percentage of participants Interval 7.0 to 26.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) Trivalent	16.4 percentage of participants Interval 8.2 to 28.1	16.4 percentage of participants Interval 8.2 to 28.1
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304) Tetravalent	70.5 percentage of participants Interval 57.4 to 81.5	65.6 percentage of participants Interval 52.3 to 77.3

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304.)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=59 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=60 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) Bivalent	15.3 percentage of participants Interval 7.2 to 27.0	0 percentage of participants Interval 0.0 to 6.0
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) Trivalent	20.3 percentage of participants Interval 11.0 to 32.8	0 percentage of participants Interval 0.0 to 6.0
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304) Tetravalent	64.4 percentage of participants Interval 50.9 to 76.4	100 percentage of participants Interval 94.0 to 100.0

PRIMARY outcome

Timeframe: Pre-booster dose at Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=41 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=39 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) Bivalent	22.0 percentage of participants Interval 10.6 to 37.6	17.9 percentage of participants Interval 7.5 to 33.5
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) Trivalent	26.8 percentage of participants Interval 14.2 to 42.9	25.6 percentage of participants Interval 13.0 to 42.1
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315) Tetravalent	51.2 percentage of participants Interval 35.1 to 67.1	48.7 percentage of participants Interval 32.4 to 65.2

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=37 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) Bivalent	22.5 percentage of participants Interval 10.8 to 38.5	0 percentage of participants Interval 0.0 to 9.5
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) Trivalent	30.0 percentage of participants Interval 16.6 to 46.5	0 percentage of participants Interval 0.0 to 9.5
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315) Tetravalent	45.0 percentage of participants Interval 29.3 to 61.5	100 percentage of participants Interval 90.5 to 100.0

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \ any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=102 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=100 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus: Positive; Bivalent	7.7 percentage of participants Interval 0.2 to 36.0	8.3 percentage of participants Interval 0.2 to 38.5
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus: Positive; Trivalent	15.4 percentage of participants Interval 1.9 to 45.4	16.7 percentage of participants Interval 2.1 to 48.4
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus: Positive; Tetravalent	76.9 percentage of participants Interval 46.2 to 95.0	66.7 percentage of participants Interval 34.9 to 90.1
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus: Negative; Bivalent	16.9 percentage of participants Interval 9.8 to 26.3	17.0 percentage of participants Interval 9.9 to 26.6
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus: Negative; Trivalent	21.3 percentage of participants Interval 13.4 to 31.3	20.5 percentage of participants Interval 12.6 to 30.4
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials Parent Trial Baseline Serostatus: Negative; Tetravalent	60.7 percentage of participants Interval 49.7 to 70.9	58.0 percentage of participants Interval 47.0 to 68.4

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \ any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=99 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=97 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus: Positive; Bivalent	8.3 percentage of participants Interval 0.2 to 38.5	0 percentage of participants Interval 0.0 to 28.5
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus: Positive; Trivalent	8.3 percentage of participants Interval 0.2 to 38.5	0 percentage of participants Interval 0.0 to 28.5
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus: Positive; Tetravalent	83.3 percentage of participants Interval 51.6 to 97.9	100 percentage of participants Interval 71.5 to 100.0
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus: Negative; Bivalent	19.5 percentage of participants Interval 11.8 to 29.4	0 percentage of participants Interval 0.0 to 4.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus: Negative; Trivalent	26.4 percentage of participants Interval 17.6 to 37.0	0 percentage of participants Interval 0.0 to 4.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials Parent Trial Baseline Serostatus: Negative; Tetravalent	52.9 percentage of participants Interval 41.9 to 63.7	100 percentage of participants Interval 95.8 to 100.0

PRIMARY outcome

Timeframe: Pre-booster dose at Month 15 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \ any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=61 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=61 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus: Positive; Bivalent	10.0 percentage of participants Interval 0.3 to 44.5	11.1 percentage of participants Interval 0.3 to 48.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus: Positive; Trivalent	20.0 percentage of participants Interval 2.5 to 55.6	0 percentage of participants Interval 0.0 to 33.6
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus: Positive; Tetravalent	70.0 percentage of participants Interval 34.8 to 93.3	77.8 percentage of participants Interval 40.0 to 97.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus: Negative; Bivalent	11.8 percentage of participants Interval 4.4 to 23.9	15.4 percentage of participants Interval 6.9 to 28.1
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus: Negative; Trivalent	15.7 percentage of participants Interval 7.0 to 28.6	19.2 percentage of participants Interval 9.6 to 32.5
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304) Parent Trial Baseline Serostatus: Negative; Tetravalent	70.6 percentage of participants Interval 56.2 to 82.5	63.5 percentage of participants Interval 49.0 to 76.4

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 16 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=59 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=60 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus: Positive; Bivalent	11.1 percentage of participants Interval 0.3 to 48.2	0 percentage of participants Interval 0.0 to 36.9
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus: Positive; Trivalent	11.1 percentage of participants Interval 0.3 to 48.2	0 percentage of participants Interval 0.0 to 36.9
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus: Positive; Tetravalent	77.8 percentage of participants Interval 40.0 to 97.2	100 percentage of participants Interval 63.1 to 100.0
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus: Negative; Bivalent	16.0 percentage of participants Interval 7.2 to 29.1	0 percentage of participants Interval 0.0 to 6.8
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus: Negative; Trivalent	22.0 percentage of participants Interval 11.5 to 36.0	0 percentage of participants Interval 0.0 to 6.8
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304) Parent Trial Baseline Serostatus: Negative; Tetravalent	62.0 percentage of participants Interval 47.2 to 75.3	100 percentage of participants Interval 93.2 to 100.0

PRIMARY outcome

Timeframe: Pre-booster dose at Month 42 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Outcome measures

Measure	Prior to Booster: DEN-304 n=41 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=39 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus: Positive; Bivalent	0 percentage of participants Interval 0.0 to 70.8	0 percentage of participants Interval 0.0 to 70.8
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus: Positive; Trivalent	0 percentage of participants Interval 0.0 to 70.8	66.7 percentage of participants Interval 9.4 to 99.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus: Positive; Tetravalent	100 percentage of participants Interval 29.2 to 100.0	33.3 percentage of participants Interval 0.8 to 90.6
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus: Negative; Bivalent	23.7 percentage of participants Interval 11.4 to 40.2	19.4 percentage of participants Interval 8.2 to 36.0
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus: Negative; Trivalent	28.9 percentage of participants Interval 15.4 to 45.9	22.2 percentage of participants Interval 10.1 to 39.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315) Parent Trial Baseline Serostatus: Negative; Tetravalent	47.4 percentage of participants Interval 31.0 to 64.2	50.0 percentage of participants Interval 32.9 to 67.1

PRIMARY outcome

Timeframe: 1 month post-booster dose at Month 43 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=37 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus: Positive; Bivalent	0 percentage of participants Interval 0.0 to 70.8	0 percentage of participants Interval 0.0 to 70.8
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus: Positive; Trivalent	0 percentage of participants Interval 0.0 to 70.8	0 percentage of participants Interval 0.0 to 70.8
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus: Positive; Tetravalent	100 percentage of participants Interval 29.2 to 100.0	100 percentage of participants Interval 29.2 to 100.0
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus: Negative; Bivalent	24.3 percentage of participants Interval 11.8 to 41.2	0 percentage of participants Interval 0.0 to 10.3
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus: Negative; Trivalent	32.4 percentage of participants Interval 18.0 to 49.8	0 percentage of participants Interval 0.0 to 10.3
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315) Parent Trial Baseline Serostatus: Negative; Tetravalent	40.5 percentage of participants Interval 24.8 to 57.9	100 percentage of participants Interval 89.7 to 100.0

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=96 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=92 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials Bivalent	14.6 percentage of participants Interval 8.2 to 23.3	2.2 percentage of participants Interval 0.3 to 7.6
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials Trivalent	21.9 percentage of participants Interval 14.1 to 31.5	5.4 percentage of participants Interval 1.8 to 12.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials Tetravalent	57.3 percentage of participants Interval 46.8 to 67.3	92.4 percentage of participants Interval 84.9 to 96.9

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=56 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=54 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) Bivalent	14.3 percentage of participants Interval 6.4 to 26.2	1.9 percentage of participants Interval 0.0 to 9.9
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) Trivalent	16.1 percentage of participants Interval 7.6 to 28.3	5.6 percentage of participants Interval 1.2 to 15.4
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304) Tetravalent	64.3 percentage of participants Interval 50.4 to 76.6	92.6 percentage of participants Interval 82.1 to 97.9

PRIMARY outcome

Timeframe: 6 months post-Booster dose at Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=38 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) Bivalent	15.0 percentage of participants Interval 5.7 to 29.8	2.6 percentage of participants Interval 0.1 to 13.8
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) Trivalent	30.0 percentage of participants Interval 16.6 to 46.5	5.3 percentage of participants Interval 0.6 to 17.7
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315) Tetravalent	47.5 percentage of participants Interval 31.5 to 63.9	92.1 percentage of participants Interval 78.6 to 98.3

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Outcome measures

Measure	Prior to Booster: DEN-304 n=96 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=92 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus: Positive; Bivalent	0 percentage of participants Interval 0.0 to 30.8	8.3 percentage of participants Interval 0.2 to 38.5
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus: Positive; Trivalent	0 percentage of participants Interval 0.0 to 30.8	16.7 percentage of participants Interval 2.1 to 48.4
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus: Positive; Tetravalent	90.0 percentage of participants Interval 55.5 to 99.7	75.0 percentage of participants Interval 42.8 to 94.5
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus: Negative; Bivalent	16.3 percentage of participants Interval 9.2 to 25.8	1.3 percentage of participants Interval 0.0 to 6.8
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus: Negative; Trivalent	24.4 percentage of participants Interval 15.8 to 34.9	3.8 percentage of participants Interval 0.8 to 10.6
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials Parent Trial Baseline Serostatus: Negative; Tetravalent	53.5 percentage of participants Interval 42.4 to 64.3	95.0 percentage of participants Interval 87.7 to 98.6

PRIMARY outcome

Timeframe: 6 months post-booster dose at Month 21 (DEN-304)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Outcome measures

Measure	Prior to Booster: DEN-304 n=56 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=54 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus: Positive; Bivalent	0 percentage of participants Interval 0.0 to 36.9	11.1 percentage of participants Interval 0.3 to 48.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus: Positive; Trivalent	0 percentage of participants Interval 0.0 to 36.9	11.1 percentage of participants Interval 0.3 to 48.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus: Positive; Tetravalent	87.5 percentage of participants Interval 47.3 to 99.7	77.8 percentage of participants Interval 40.0 to 97.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus: Negative; Bivalent	16.7 percentage of participants Interval 7.5 to 30.2	0 percentage of participants Interval 0.0 to 7.9
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus: Negative; Trivalent	18.8 percentage of participants Interval 8.9 to 32.6	4.4 percentage of participants Interval 0.5 to 15.1
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304) Parent Trial Baseline Serostatus: Negative; Tetravalent	60.4 percentage of participants Interval 45.3 to 74.2	95.6 percentage of participants Interval 84.9 to 99.5

PRIMARY outcome

Timeframe: 6 months post-Booster dose at Month 48 (DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Overall number of participants analyzed: number of participants with data available for analyses. Number analyzed: number of participants with data available for analysis for the specified category.

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Outcome measures

Measure	Prior to Booster: DEN-304 n=40 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=38 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus: Positive; Bivalent	0 percentage of participants Interval 0.0 to 84.2	0 percentage of participants Interval 0.0 to 70.8
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus: Positive; Trivalent	0 percentage of participants Interval 0.0 to 84.2	33.3 percentage of participants Interval 0.8 to 90.6
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus: Positive; Tetravalent	100 percentage of participants Interval 15.8 to 100.0	66.7 percentage of participants Interval 9.4 to 99.2
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus: Negative; Bivalent	15.8 percentage of participants Interval 6.0 to 31.3	2.9 percentage of participants Interval 0.1 to 14.9
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus: Negative; Trivalent	31.6 percentage of participants Interval 17.5 to 48.7	2.9 percentage of participants Interval 0.1 to 14.9
Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315) Parent Trial Baseline Serostatus: Negative; Tetravalent	44.7 percentage of participants Interval 28.6 to 61.7	94.3 percentage of participants Interval 80.8 to 99.3

SECONDARY outcome

Timeframe: Month 12 vs Month 0, Month 15 (DEN-304) vs parent trial Month 4, Mont 42 (DEN315) vs parent trial Month 4, Month 0 vs parent trial Month 9, Month 12 vs parent trial Month 9

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Number analyzed: number of participants with data available for analysis for the specified category.

The geometric mean ratio is the geometric mean of the ratio of the two visits being compared.

Outcome measures

Measure	Prior to Booster: DEN-304 n=239 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 12 vs Month 0: DENV-1	0.753 unitless ratio Interval 0.675 to 0.84	0.891 unitless ratio Interval 0.741 to 1.071
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 12 vs Month 0: DENV-2	0.698 unitless ratio Interval 0.65 to 0.749	0.622 unitless ratio Interval 0.548 to 0.705
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 12 vs Month 0: DENV-3	0.864 unitless ratio Interval 0.791 to 0.945	0.852 unitless ratio Interval 0.668 to 1.088
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 12 vs Month 0: DENV-4	0.689 unitless ratio Interval 0.632 to 0.751	0.861 unitless ratio Interval 0.708 to 1.046
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 15 (DEN-304) vs Parent Trial Month 4: DENV-1	0.438 unitless ratio Interval 0.382 to 0.502	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 15 (DEN-304) vs Parent Trial Month 4: DENV-2	0.159 unitless ratio Interval 0.137 to 0.185	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 15 (DEN-304) vs Parent Trial Month 4: DENV-3	0.275 unitless ratio Interval 0.241 to 0.315	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 15 (DEN-304) vs Parent Trial Month 4: DENV-4	0.216 unitless ratio Interval 0.183 to 0.255	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 42 (DEN-315) vs Parent Trial Month 4: DENV-1	—	0.296 unitless ratio Interval 0.24 to 0.366
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 42 (DEN-315) vs Parent Trial Month 4: DENV-2	—	0.108 unitless ratio Interval 0.089 to 0.13
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 42 (DEN-315) vs Parent Trial Month 4: DENV-3	—	0.202 unitless ratio Interval 0.162 to 0.252
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 42 (DEN-315) vs Parent Trial Month 4: DENV-4	—	0.066 unitless ratio Interval 0.055 to 0.079
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 0 vs Parent Trial Month 9: DENV-1	0.529 unitless ratio Interval 0.482 to 0.582	0.517 unitless ratio Interval 0.455 to 0.587
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 0 vs Parent Trial Month 9: DENV-2	0.396 unitless ratio Interval 0.369 to 0.426	0.466 unitless ratio Interval 0.415 to 0.522
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 0 vs Parent Trial Month 9: DENV-3	0.440 unitless ratio Interval 0.394 to 0.492	0.547 unitless ratio Interval 0.477 to 0.629
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 0 vs Parent Trial Month 9: DENV-4	0.577 unitless ratio Interval 0.518 to 0.641	0.568 unitless ratio Interval 0.504 to 0.641
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 12 vs Parent Trial Month 9: DENV-1	0.415 unitless ratio Interval 0.367 to 0.47	0.486 unitless ratio Interval 0.377 to 0.627
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 12 vs Parent Trial Month 9: DENV-2	0.265 unitless ratio Interval 0.239 to 0.295	0.289 unitless ratio Interval 0.238 to 0.351
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 12 vs Parent Trial Month 9: DENV-3	0.407 unitless ratio Interval 0.353 to 0.47	0.435 unitless ratio Interval 0.336 to 0.562
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose Month 12 vs Parent Trial Month 9: DENV-4	0.384 unitless ratio Interval 0.335 to 0.44	0.567 unitless ratio Interval 0.431 to 0.745

SECONDARY outcome

Timeframe: Month 12 vs Month 0, Month 15 (DEN-304) vs parent trial Month 4, Month 42 (DEN315) vs parent trial Month 4, Month 0 vs parent trial Month 9, Month 12 vs parent trial Month 9

Population: PPS included all participants from the FAS who received two doses of Takeda's TDV in the parent trials with no new major protocol violations in this trial prior to administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Number analyzed: number of participants with data available for analysis for the specified category.

The geometric mean ratio is the geometric mean of the ratio of the two visits being compared. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial.

Outcome measures

Measure	Prior to Booster: DEN-304 n=239 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 12 vs Month 0: DENV-1	0.736 unitless ratio Interval 0.556 to 0.974	0.705 unitless ratio Interval 0.002 to 222.445
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 12 vs Month 0: DENV-2	0.756 unitless ratio Interval 0.599 to 0.955	0.456 unitless ratio Interval 0.056 to 3.733
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 12 vs Month 0: DENV-3	0.980 unitless ratio Interval 0.834 to 1.152	1.000 unitless ratio The confidence interval was not estimable due to an observed standard deviation of 0.
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 12 vs Month 0: DENV-4	0.736 unitless ratio Interval 0.598 to 0.906	0.727 unitless ratio Interval 0.064 to 8.28
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 15 (DEN-304) vs Parent Trial Month 4: DENV-1	0.506 unitless ratio Interval 0.349 to 0.733	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 15 (DEN-304) vs Parent Trial Month 4: DENV-2	0.164 unitless ratio Interval 0.108 to 0.249	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 15 (DEN-304) vs Parent Trial Month 4: DENV-3	0.350 unitless ratio Interval 0.238 to 0.514	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 15 (DEN-304) vs Parent Trial Month 4: DENV-4	0.178 unitless ratio Interval 0.125 to 0.253	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 42 (DEN-315) vs Parent Trial Month 4: DENV-1	—	0.393 unitless ratio Interval 0.155 to 0.998
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 42 (DEN-315) vs Parent Trial Month 4: DENV-2	—	0.164 unitless ratio Interval 0.066 to 0.408
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 42 (DEN-315) vs Parent Trial Month 4: DENV-3	—	0.319 unitless ratio Interval 0.204 to 0.499
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 42 (DEN-315) vs Parent Trial Month 4: DENV-4	—	0.070 unitless ratio Interval 0.036 to 0.138
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 0 vs Parent Trial Month 9: DENV-1	0.635 unitless ratio Interval 0.467 to 0.864	0.528 unitless ratio Interval 0.453 to 0.616
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 0 vs Parent Trial Month 9: DENV-2	0.469 unitless ratio Interval 0.356 to 0.619	0.454 unitless ratio Interval 0.312 to 0.661
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 0 vs Parent Trial Month 9: DENV-3	0.538 unitless ratio Interval 0.361 to 0.801	0.556 unitless ratio Interval 0.356 to 0.868
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 0 vs Parent Trial Month 9: DENV-4	0.710 unitless ratio Interval 0.475 to 1.062	0.684 unitless ratio Interval 0.401 to 1.165
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 12 vs Parent Trial Month 9: DENV-1	0.497 unitless ratio Interval 0.33 to 0.748	0.375 unitless ratio Interval 0.0 to 400.159
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 12 vs Parent Trial Month 9: DENV-2	0.311 unitless ratio Interval 0.203 to 0.477	0.172 unitless ratio Interval 0.161 to 0.184
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 12 vs Parent Trial Month 9: DENV-3	0.561 unitless ratio Interval 0.329 to 0.957	0.664 unitless ratio Interval 0.004 to 119.652
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Positive; Month 12 vs Parent Trial Month 9: DENV-4	0.577 unitless ratio Interval 0.335 to 0.994	0.966 unitless ratio Interval 0.005 to 194.455
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 12 vs Month 0; DENV-1	0.756 unitless ratio Interval 0.671 to 0.851	0.900 unitless ratio Interval 0.745 to 1.088
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 12 vs Month 0; DENV-2	0.689 unitless ratio Interval 0.639 to 0.742	0.630 unitless ratio Interval 0.553 to 0.718
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 12 vs Month 0; DENV-3	0.847 unitless ratio Interval 0.767 to 0.936	0.846 unitless ratio Interval 0.656 to 1.092
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 12 vs Month 0; DENV-4	0.681 unitless ratio Interval 0.619 to 0.75	0.867 unitless ratio Interval 0.708 to 1.063
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 15 (DEN-304) vs Parent Trial Month 4; DENV-1	0.427 unitless ratio Interval 0.368 to 0.496	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 15 (DEN-304) vs Parent Trial Month 4; DENV-2	0.158 unitless ratio Interval 0.135 to 0.186	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 15 (DEN-304) vs Parent Trial Month 4; DENV-3	0.265 unitless ratio Interval 0.229 to 0.305	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 15 (DEN-304) vs Parent Trial Month 4; DENV-4	0.223 unitless ratio Interval 0.186 to 0.268	—
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 42 (DEN-315) vs Parent Trial Month 4; DENV-1	—	0.288 unitless ratio Interval 0.231 to 0.359
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 42 (DEN-315) vs Parent Trial Month 4; DENV-2	—	0.103 unitless ratio Interval 0.085 to 0.125
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 42 (DEN-315) vs Parent Trial Month 4; DENV-3	—	0.192 unitless ratio Interval 0.152 to 0.244
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 42 (DEN-315) vs Parent Trial Month 4; DENV-4	—	0.065 unitless ratio Interval 0.053 to 0.08
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 0 vs Parent Trial Month 9; DENV-1	0.514 unitless ratio Interval 0.466 to 0.567	0.516 unitless ratio Interval 0.45 to 0.592
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 0 vs Parent Trial Month 9; DENV-2	0.385 unitless ratio Interval 0.359 to 0.414	0.467 unitless ratio Interval 0.413 to 0.527
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 0 vs Parent Trial Month 9; DENV-3	0.426 unitless ratio Interval 0.381 to 0.477	0.547 unitless ratio Interval 0.472 to 0.633
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 0 vs Parent Trial Month 9; DENV-4	0.557 unitless ratio Interval 0.501 to 0.619	0.560 unitless ratio Interval 0.494 to 0.634
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 12 vs Parent Trial Month 9; DENV-1	0.403 unitless ratio Interval 0.354 to 0.459	0.492 unitless ratio Interval 0.378 to 0.641
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 12 vs Parent Trial Month 9; DENV-2	0.259 unitless ratio Interval 0.233 to 0.287	0.296 unitless ratio Interval 0.242 to 0.362
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 12 vs Parent Trial Month 9; DENV-3	0.387 unitless ratio Interval 0.335 to 0.446	0.426 unitless ratio Interval 0.327 to 0.556
Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose Parent Trial Baseline Serostatus: Negative; Month 12 vs Parent Trial Month 9; DENV-4	0.359 unitless ratio Interval 0.315 to 0.41	0.553 unitless ratio Interval 0.416 to 0.734

SECONDARY outcome

Timeframe: Months (M) 1&6 post-booster dose in current trial vs M 4 in parent trials; post-booster M 6 vs post-booster M 1; post-booster M 1 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315); post-booster M 6 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315)

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Number analyzed: number of participants with data available for analysis for the specified category.

The geometric mean ratio is the geometric mean of the ratio of the two visits being compared.

Outcome measures

Measure	Prior to Booster: DEN-304 n=102 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=100 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Pre-booster dose: DENV-1	0.784 unitless ratio Interval 0.699 to 0.879	3.810 unitless ratio Interval 2.847 to 5.097
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 1 vs Parent Trial Month 4: DENV-1	0.352 unitless ratio Interval 0.296 to 0.417	4.298 unitless ratio Interval 3.204 to 5.767
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 1 vs Parent Trial Month 4: DENV-2	0.124 unitless ratio Interval 0.107 to 0.144	0.378 unitless ratio Interval 0.285 to 0.502
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 1 vs Parent Trial Month 4: DENV-3	0.231 unitless ratio Interval 0.188 to 0.284	3.042 unitless ratio Interval 2.217 to 4.175
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 1 vs Parent Trial Month 4: DENV-4	0.136 unitless ratio Interval 0.107 to 0.174	1.505 unitless ratio Interval 1.093 to 2.072
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Parent Trial Month 4: DENV-1	0.285 unitless ratio Interval 0.235 to 0.345	1.409 unitless ratio Interval 1.036 to 1.917
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Parent Trial Month 4: DENV-2	0.100 unitless ratio Interval 0.086 to 0.117	0.206 unitless ratio Interval 0.158 to 0.269
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Parent Trial Month 4:DENV-3	0.225 unitless ratio Interval 0.187 to 0.272	1.133 unitless ratio Interval 0.816 to 1.573
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Parent Trial Month 4: DENV-4	0.110 unitless ratio Interval 0.088 to 0.137	0.468 unitless ratio Interval 0.345 to 0.635
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Booster Month 1: DENV-1	0.817 unitless ratio Interval 0.73 to 0.914	0.334 unitless ratio Interval 0.283 to 0.395
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Booster Month 1: DENV-2	0.825 unitless ratio Interval 0.753 to 0.903	0.535 unitless ratio Interval 0.452 to 0.634
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Booster Month 1: DENV-3	0.990 unitless ratio Interval 0.894 to 1.096	0.370 unitless ratio Interval 0.295 to 0.463
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Booster Month 1: DENV-4	0.842 unitless ratio Interval 0.744 to 0.954	0.323 unitless ratio Interval 0.263 to 0.396
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 1 vs Pre-booster dose: DENV-1	0.962 unitless ratio Interval 0.879 to 1.053	11.762 unitless ratio Interval 8.66 to 15.975
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 1 vs Pre-booster dose: DENV-2	0.936 unitless ratio Interval 0.862 to 1.016	2.822 unitless ratio Interval 2.208 to 3.607
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 1 vs Pre-booster dose: DENV-3	0.856 unitless ratio Interval 0.773 to 0.948	14.889 unitless ratio Interval 10.992 to 20.17
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 1 vs Pre-booster dose: DENV-4	0.977 unitless ratio Interval 0.855 to 1.117	13.162 unitless ratio Interval 9.443 to 18.345
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Pre-booster dose: DENV-2	0.763 unitless ratio Interval 0.697 to 0.835	1.550 unitless ratio Interval 1.25 to 1.923
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Pre-booster dose: DENV-3	0.858 unitless ratio Interval 0.767 to 0.96	5.622 unitless ratio Interval 4.151 to 7.614
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase Booster Month 6 vs Pre-booster dose: DENV-4	0.808 unitless ratio Interval 0.703 to 0.929	4.289 unitless ratio Interval 3.205 to 5.741

SECONDARY outcome

Timeframe: Months (M) 1&6 post-booster dose in current trial vs M 4 in parent trials; post-booster M 1 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315); post-booster M 6 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315); post-booster M 6 vs post-booster M 1

Population: PPS-B included all participants from the FAS-B who received two doses of Takeda's TDV in the parent trials with no new major protocol violations after administration of the trial vaccination at Visit 3 that could potentially confound the primary endpoints in the current trial. Number analyzed: number of participants with data available for analysis for the specified category.

The geometric mean ratio is the geometric mean of the ratio of the two visits being compared. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial.

Outcome measures

Measure	Prior to Booster: DEN-304 n=102 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=100 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 1 vs Parent Trial Month 4: DENV-1	0.413 unitless ratio Interval 0.236 to 0.721	2.219 unitless ratio Interval 1.181 to 4.169
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 1 vs Parent Trial Month 4: DENV-2	0.118 unitless ratio Interval 0.077 to 0.18	0.355 unitless ratio Interval 0.203 to 0.62
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 1 vs Parent Trial Month 4: DENV-3	0.311 unitless ratio Interval 0.186 to 0.52	1.566 unitless ratio Interval 0.684 to 3.583
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 1 vs Parent Trial Month 4: DENV-4	0.187 unitless ratio Interval 0.111 to 0.315	1.018 unitless ratio Interval 0.539 to 1.922
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 1 vs Pre-booster dose: DENV-1	1.033 unitless ratio Interval 0.833 to 1.28	3.683 unitless ratio Interval 1.612 to 8.412
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 1 vs Pre-booster dose: DENV-2	0.803 unitless ratio Interval 0.615 to 1.049	1.805 unitless ratio Interval 1.311 to 2.485
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 1 vs Pre-booster dose: DENV-3	0.825 unitless ratio Interval 0.58 to 1.174	3.699 unitless ratio Interval 1.738 to 7.873
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 1 vs Pre-booster dose: DENV-4	1.310 unitless ratio Interval 0.754 to 2.279	5.895 unitless ratio Interval 2.657 to 13.078
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Pre-booster dose: DENV-1	1.065 unitless ratio Interval 0.673 to 1.686	1.404 unitless ratio Interval 0.787 to 2.506
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Pre-booster dose: DENV-2	0.739 unitless ratio Interval 0.48 to 1.137	0.906 unitless ratio Interval 0.673 to 1.221
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Pre-booster dose: DENV-3	0.965 unitless ratio Interval 0.733 to 1.271	1.544 unitless ratio Interval 0.868 to 2.748
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Pre-booster dose: DENV-4	0.871 unitless ratio Interval 0.492 to 1.543	1.923 unitless ratio Interval 0.941 to 3.931
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Booster Month 1: DENV-1	0.998 unitless ratio Interval 0.742 to 1.343	0.379 unitless ratio Interval 0.221 to 0.65
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Booster Month 1: DENV-2	1.026 unitless ratio Interval 0.713 to 1.475	0.506 unitless ratio Interval 0.33 to 0.775
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Booster Month 1: DENV-3	1.024 unitless ratio Interval 0.821 to 1.278	0.437 unitless ratio Interval 0.255 to 0.75
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Booster Month 1: DENV-4	0.772 unitless ratio Interval 0.462 to 1.292	0.349 unitless ratio Interval 0.204 to 0.597
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Parent Trial Month 4: DENV-1	0.400 unitless ratio Interval 0.175 to 0.915	0.779 unitless ratio Interval 0.379 to 1.599
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Parent Trial Month 4: DENV-2	0.103 unitless ratio Interval 0.066 to 0.162	0.161 unitless ratio Interval 0.086 to 0.304
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Parent Trial Month 4:DENV-3	0.333 unitless ratio Interval 0.215 to 0.515	0.593 unitless ratio Interval 0.267 to 1.321
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Positive; Booster Month 6 vs Parent Trial Month 4: DENV-4	0.113 unitless ratio Interval 0.063 to 0.201	0.314 unitless ratio Interval 0.134 to 0.735
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 1 vs Parent Trial Month 4; DENV-1	0.343 unitless ratio Interval 0.286 to 0.413	4.692 unitless ratio Interval 3.404 to 6.467
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 1 vs Parent Trial Month 4; DENV-2	0.125 unitless ratio Interval 0.106 to 0.147	0.382 unitless ratio Interval 0.278 to 0.523
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 1 vs Parent Trial Month 4; DENV-3	0.221 unitless ratio Interval 0.177 to 0.277	3.322 unitless ratio Interval 2.359 to 4.678
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 1 vs Parent Trial Month 4; DENV-4	0.130 unitless ratio Interval 0.099 to 0.171	1.585 unitless ratio Interval 1.112 to 2.259
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 1 vs Pre-booster dose; DENV-1	0.953 unitless ratio Interval 0.862 to 1.053	13.646 unitless ratio Interval 9.906 to 18.796
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 1 vs Pre-booster dose; DENV-2	0.956 unitless ratio Interval 0.876 to 1.043	2.988 unitless ratio Interval 2.275 to 3.925
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 1 vs Pre-booster dose; DENV-3	0.860 unitless ratio Interval 0.771 to 0.959	17.792 unitless ratio Interval 13.012 to 24.329
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 1 vs Pre-booster dose; DENV-4	0.939 unitless ratio Interval 0.82 to 1.074	14.586 unitless ratio Interval 10.186 to 20.888
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Pre-booster dose; DENV-1	0.756 unitless ratio Interval 0.672 to 0.851	4.425 unitless ratio Interval 3.233 to 6.056
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Pre-booster dose; DENV-2	0.766 unitless ratio Interval 0.698 to 0.84	1.680 unitless ratio Interval 1.321 to 2.137
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Pre-booster dose; DENV-3	0.846 unitless ratio Interval 0.749 to 0.957	6.824 unitless ratio Interval 4.957 to 9.395
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Pre-booster dose; DENV-4	0.801 unitless ratio Interval 0.692 to 0.926	4.837 unitless ratio Interval 3.533 to 6.623
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Booster Month 1; DENV-1	0.799 unitless ratio Interval 0.709 to 0.902	0.328 unitless ratio Interval 0.274 to 0.393
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Booster Month 1; DENV-2	0.805 unitless ratio Interval 0.733 to 0.885	0.539 unitless ratio Interval 0.447 to 0.65
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Booster Month 1; DENV-3	0.986 unitless ratio Interval 0.882 to 1.103	0.361 unitless ratio Interval 0.282 to 0.463
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Booster Month 1; DENV-4	0.850 unitless ratio Interval 0.746 to 0.969	0.319 unitless ratio Interval 0.255 to 0.399
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Parent Trial Month 4; DENV-1	0.273 unitless ratio Interval 0.224 to 0.333	1.546 unitless ratio Interval 1.102 to 2.168
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Parent Trial Month 4; DENV-2	0.100 unitless ratio Interval 0.085 to 0.118	0.214 unitless ratio Interval 0.16 to 0.288
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Parent Trial Month 4; DENV-3	0.215 unitless ratio Interval 0.175 to 0.263	1.253 unitless ratio Interval 0.875 to 1.795
GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase Parent Trial Baseline Serostatus: Negative; Booster Month 6 vs Parent Trial Month 4; DENV-4	0.109 unitless ratio Interval 0.086 to 0.139	0.498 unitless ratio Interval 0.357 to 0.694

SECONDARY outcome

Timeframe: Days 1 through 7 post-booster dose at Visit 3 (Month 15 [DEN-304]) and (Month 42 [DEN-315])

Population: Safety Set-Booster (SAF-B) included all participants who received at least one dose of Takeda's TDV in the parent trials and who received the trial vaccination in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Solicited local AEs at injection site are defined as pain, erythema and swelling that occurred within 7 days post-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315). AEs were graded by the investigator in the following manner: Mild: Grade 1: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities. Relieved with or without symptomatic treatment; Moderate: Grade 2: Sufficient discomfort is present to cause interference with normal activity. Only partially relieved with symptomatic treatment; Severe: Grade 3: Extreme distress, causing significant impairment of functioning or incapacitation. Prevents normal everyday activities. Not relieved with symptomatic treatment.

Outcome measures

Measure	Prior to Booster: DEN-304 n=115 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=112 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post-Booster Vaccination Mild	17.4 percentage of participants	50.0 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post-Booster Vaccination Moderate	5.2 percentage of participants	14.3 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post-Booster Vaccination Severe	0 percentage of participants	1.8 percentage of participants

SECONDARY outcome

Timeframe: Days 1 through 14 post-booster dose at Visit 3 (Month 15 [DEN-304]) and (Month 42 [DEN-315])

Population: SAF-B included all participants who received at least one dose of Takeda's TDV in the parent trials and who received the trial vaccination in the current trial. Overall number of participants analyzed: number of participants with data available for analyses.

Solicited systemic AEs are defined as fever, headache, asthenia, malaise and myalgia that occurred within 14 days post-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315). AEs were graded by the investigator in the following manner: Mild: Grade 1: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities. Relieved with or without symptomatic treatment; Moderate: Grade 2: Sufficient discomfort is present to cause interference with normal activity. Only partially relieved with symptomatic treatment; Severe: Grade 3: Extreme distress, causing significant impairment of functioning or incapacitation. Prevents normal everyday activities. Not relieved with symptomatic treatment.

Outcome measures

Measure	Prior to Booster: DEN-304 n=115 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=112 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Percentage of Participants With Solicited Systemic Adverse Events Within 14 Days Post-Booster Vaccination by Severity Mild	30.4 percentage of participants	32.1 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events Within 14 Days Post-Booster Vaccination by Severity Moderate	12.2 percentage of participants	17.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events Within 14 Days Post-Booster Vaccination by Severity Severe	1.7 percentage of participants	3.6 percentage of participants

SECONDARY outcome

Timeframe: Days 1 through 28 post-booster dose at Visit 3 (Month 15 [DEN-304]) and (Month 42 [DEN-315])

Population: SAF-B included all participants who received at least one dose of Takeda's TDV in the parent trials and who received the trial vaccination in the current trial.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine or placebo; it does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Measure	Prior to Booster: DEN-304 n=118 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=115 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Percentage of Participants With Any Unsolicited AEs in the Booster Phase	6.8 percentage of participants	6.1 percentage of participants

SECONDARY outcome

Timeframe: Month 15 post-booster dose through Month 21 (DEN-304); Month 42 post-booster dose through Month 48 (DEN-315)

Population: SAF-B included all participants who received at least one dose of Takeda's TDV in the parent trials and who received the trial vaccination in the current trial.

MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria.

Outcome measures

Measure	Prior to Booster: DEN-304 n=118 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=115 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Percentage of Participants With Any Medically Attended AEs (MAAEs) in the Booster Phase	16.9 percentage of participants	11.3 percentage of participants

SECONDARY outcome

Timeframe: Month 0 through Month 15 (DEN-304) and Month 42 (DEN-315)

Population: SAF included all participants who agreed to participate in the current trial, did not screen fail, and who received at least one dose of Takeda's TDV in the parent trials.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine or placebo; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important event.

Outcome measures

Measure	Prior to Booster: DEN-304 n=246 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Percentage of Participants With Any Serious Adverse Events (SAEs) Prior to the Booster Dose	2.4 percentage of participants	6.7 percentage of participants

SECONDARY outcome

Timeframe: Month 15 post-booster dose after vaccination through Month 21 (DEN-304); Month 42 post-booster dose after vaccination through Month 48 (DEN-315)

Population: SAF-B included all participants who received at least one dose of Takeda's TDV in the parent trials and who received the trial vaccination in the current trial.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine or placebo; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important event.

Outcome measures

Measure	Prior to Booster: DEN-304 n=118 Participants Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=115 Participants Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).
Percentage of Participants With Any SAEs in the Booster Phase	2.5 percentage of participants	0 percentage of participants

Adverse Events

Prior to Booster: DEN-304

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Prior to Booster: DEN-315

Serious events: 8 serious events

Other events: 0 other events

Deaths: 1 deaths

Booster Phase: TDV

Serious events: 0 serious events

Other events: 83 other events

Deaths: 0 deaths

Booster Phase: Placebo

Serious events: 3 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Measure	Prior to Booster: DEN-304 n=246 participants at risk Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 participants at risk Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).	Booster Phase: TDV n=115 participants at risk Participants received TDV 0.5 mL, injection, subcutaneously, once at Month 15 for participants from parent trials DEN-304 (US) or once at Month 42 for participants from parent trial DEN-315 (Mexico).	Booster Phase: Placebo n=118 participants at risk Participants received TDV placebo-matching 0.5 mL injection, subcutaneously, once at Month 15 for participants from parent trial DEN-304 (US) or once at Month 42 for participants from parent trial DEN-315 (Mexico).
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.84% 1/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.85% 1/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Cardiac disorders Acute coronary syndrome	0.41% 1/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Cardiac disorders Acute myocardial infarction	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.85% 1/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Infections and infestations Appendicitis	0.41% 1/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.84% 1/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.41% 1/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Metabolism and nutrition disorders Dehydration	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.84% 1/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Injury, poisoning and procedural complications Fall	0.41% 1/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.85% 1/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.41% 1/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.84% 1/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Infections and infestations Mastitis	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.84% 1/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.41% 1/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Infections and infestations Pilonidal disease	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.84% 1/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Infections and infestations Pneumonia bacterial	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.84% 1/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.41% 1/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Psychiatric disorders Psychotic disorder	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.84% 1/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Injury, poisoning and procedural complications Rib fracture	0.41% 1/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Pregnancy, puerperium and perinatal conditions Uterine atony	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	1.7% 2/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.

Other adverse events

Measure	Prior to Booster: DEN-304 n=246 participants at risk Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 15).	Prior to Booster: DEN-315 n=119 participants at risk Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Visit 3 (Month 42).	Booster Phase: TDV n=115 participants at risk Participants received TDV 0.5 mL, injection, subcutaneously, once at Month 15 for participants from parent trials DEN-304 (US) or once at Month 42 for participants from parent trial DEN-315 (Mexico).	Booster Phase: Placebo n=118 participants at risk Participants received TDV placebo-matching 0.5 mL injection, subcutaneously, once at Month 15 for participants from parent trial DEN-304 (US) or once at Month 42 for participants from parent trial DEN-315 (Mexico).
General disorders Asthenia	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	24.3% 28/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	18.6% 22/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	25.2% 29/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Nervous system disorders Headache	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	36.5% 42/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	32.2% 38/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
General disorders Injection site erythema	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	7.0% 8/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	1.7% 2/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
General disorders Malaise	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	24.3% 28/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	19.5% 23/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	34.8% 40/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	18.6% 22/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
General disorders Pain	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	60.9% 70/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	22.0% 26/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
General disorders Swelling	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	13.9% 16/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.
Infections and infestations Upper respiratory tract infection	0.00% 0/246 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	0.00% 0/119 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	4.3% 5/115 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.	5.1% 6/118 • All-cause mortality & SAEs: From Day 1 [Month 0] up to Month 21 (DEN-304) & Month 48 (DEN-315); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Months 15 (DEN-304) & 42 (DEN-315). Prior to Booster Arms: SAF included all participants who agreed to participate in current trial,did not screen fail\& who received at least 1 dose of Takeda's TDV in parent trials. Booster Phase Arms: SAF-B included all participants who received at least 1 dose of Takeda's TDV in parent trials \&who received the trial vaccination in current trial.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: TrialDisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place