Trial Outcomes & Findings for Pediatric Safety and Immunogenicity Study of Cell-Culture Derived and Egg-based Subunit Influenza Vaccines in Healthy Children and Adolescents (NCT NCT00645411)

NCT ID: NCT00645411

Last Updated: 2015-11-23

Results Overview

To demonstrate non-inferiority of the post vaccination hemagglutination inhibition (HI) geometric mean titer (GMT) of the cell culture-derived influenza (cTIV) vaccine to the corresponding GMT of the egg-derived (eTIV) influenza vaccine, for all three strains, after two injections administered four weeks apart to a subset of children 3 to 8 years of age. GMTs were evaluated using two assays, HI egg derived antigen assay and HI cell derived antigen assay.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 3604 participants
• Primary outcome timeframe: Day 50 post vaccination
• Results posted on: 2015-11-23

Participant Flow

Participants were enrolled from 14 sites in Finland, 16 in the US, 9 in Croatia, 5 in Italy, 6 in Lithuania, 2 in Romania, 8 in Hungary.

All subjects enrolled were included in the trial.

Participant milestones

Measure	Cohort 1+2 cTIV (9-17 Years) All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine.	Cohort 1+2 eTIV (9-17 Years) All subjects aged 9-17 years received one 0.5 mL injection, of egg -derived trivalent influenza vaccine.	Cohort 3 cTIV (3-8 Years) All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine.
Overall Study STARTED	656	318	1608	1022
Overall Study COMPLETED	643	312	1457	919
Overall Study NOT COMPLETED	13	6	151	103

Reasons for withdrawal

Measure	Cohort 1+2 cTIV (9-17 Years) All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine.	Cohort 1+2 eTIV (9-17 Years) All subjects aged 9-17 years received one 0.5 mL injection, of egg -derived trivalent influenza vaccine.	Cohort 3 cTIV (3-8 Years) All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine.
Overall Study Adverse Event	0	0	0	2
Overall Study Withdrawal by Subject	2	1	19	21
Overall Study Lost to Follow-up	10	5	124	75
Overall Study Protocol Violation	1	0	1	0
Overall Study Inappropriate enrollment	0	0	4	1
Overall Study Unable to classify	0	0	3	4

Baseline Characteristics

Pediatric Safety and Immunogenicity Study of Cell-Culture Derived and Egg-based Subunit Influenza Vaccines in Healthy Children and Adolescents

Baseline characteristics by cohort

Measure	Cohort 1+2 cTIV (9-17 Years) n=656 Participants All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine.	Cohort 1+2 eTIV (9-17 Years) n=318 Participants All subjects aged 9-17 years received one 0.5 mL injection, of egg-derived trivalent influenza vaccine.	Cohort 3 cTIV (3-8 Years) n=1608 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=1022 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine.	Total n=3604 Participants Total of all reporting groups
Age, Continuous	12.6 years STANDARD_DEVIATION 2.6 • n=5 Participants	12.6 years STANDARD_DEVIATION 2.5 • n=7 Participants	5.5 years STANDARD_DEVIATION 1.7 • n=5 Participants	5.4 years STANDARD_DEVIATION 1.7 • n=4 Participants	7.4 years STANDARD_DEVIATION 3.7 • n=21 Participants
Sex: Female, Male Female	304 Participants n=5 Participants	154 Participants n=7 Participants	795 Participants n=5 Participants	494 Participants n=4 Participants	1747 Participants n=21 Participants
Sex: Female, Male Male	352 Participants n=5 Participants	164 Participants n=7 Participants	813 Participants n=5 Participants	528 Participants n=4 Participants	1857 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 50 post vaccination

Population: The analysis was performed on the per-protocol dataset

To demonstrate non-inferiority of the post vaccination hemagglutination inhibition (HI) geometric mean titer (GMT) of the cell culture-derived influenza (cTIV) vaccine to the corresponding GMT of the egg-derived (eTIV) influenza vaccine, for all three strains, after two injections administered four weeks apart to a subset of children 3 to 8 years of age.

GMTs were evaluated using two assays, HI egg derived antigen assay and HI cell derived antigen assay.

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=524 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=513 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children A/H1N1 (egg derived antigen assay)	407 Titers Interval 358.0 to 462.0	477 Titers Interval 419.0 to 542.0
Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children A/H3N2 (egg derived antigen assay)	768 Titers Interval 666.0 to 885.0	1293 Titers Interval 1121.0 to 1491.0
Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children B (egg derived antigen assay)	25 Titers Interval 21.0 to 29.0	44 Titers Interval 38.0 to 51.0
Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children A/H1N1 (cell derived antigen assay) (N=522,513)	563 Titers Interval 501.0 to 634.0	610 Titers Interval 542.0 to 686.0
Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children A/H3N2 (cell derived antigen assay) (N=522,513)	858 Titers Interval 744.0 to 990.0	1329 Titers Interval 1152.0 to 1533.0
Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children B (cell derived antigen assay) (N=522,513)	53 Titers Interval 46.0 to 62.0	62 Titers Interval 53.0 to 72.0

PRIMARY outcome

Timeframe: Day 50 post vaccination

Population: The analysis was performed on the per-protocol dataset

To demonstrate non-inferiority of the cell culture-derived influenza (cTIV) vaccine to the egg-derived (eTIV) influenza vaccine in the percentage of subjects achieving seroconversion or significant increase in antibody titer post vaccination, for all three strains, after two injections administered four weeks apart in children 3 to 8 years of age.

Seroconversion rate was evaluated using two assays- HI egg derived antigen assay and HI cell derived antigen assay.

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=524 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=513 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children A/H1N1 (egg derived antigen assay)	94 Percentages of subjects Interval 92.0 to 96.0	96 Percentages of subjects Interval 94.0 to 97.0
Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children A/H3N2 (egg derived antigen assay)	77 Percentages of subjects Interval 73.0 to 81.0	86 Percentages of subjects Interval 82.0 to 89.0
Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children B (egg derived antigen assay)	38 Percentages of subjects Interval 34.0 to 42.0	53 Percentages of subjects Interval 49.0 to 58.0
Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children A/H1N1 (cell derived antigen assay) (N=522,513)	96 Percentages of subjects Interval 93.0 to 97.0	96 Percentages of subjects Interval 94.0 to 98.0
Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children A/H3N2 (cell derived antigen assay) (N=522,513)	80 Percentages of subjects Interval 76.0 to 83.0	85 Percentages of subjects Interval 82.0 to 88.0
Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children B (cell derived antigen assay) (N=522,513)	58 Percentages of subjects Interval 54.0 to 63.0	58 Percentages of subjects Interval 54.0 to 63.0

SECONDARY outcome

Timeframe: Day 29 post vaccination

Population: The analysis was performed on the per-protocol dataset.

To evaluate immunogenicity in terms of Geometric Mean Titers (GMTs) in children 9 to 17 years of age after one injection of either cTIV vaccine or eTIV.

GMTs were evaluated using two assays, HI egg derived antigen assay and HI cell derived antigen assay.

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=142 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=144 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Baseline (A/H1N1) egg derived antigen assay	55 Titers Interval 42.0 to 72.0	78 Titers Interval 60.0 to 101.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (A/H1N1) egg derived antigen assay	879 Titers Interval 728.0 to 1062.0	1107 Titers Interval 918.0 to 1334.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Baseline (A/H3N2) egg derived antigen assay	121 Titers Interval 94.0 to 155.0	151 Titers Interval 118.0 to 193.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (A/H3N2) egg derived antigen assay	706 Titers Interval 607.0 to 821.0	1857 Titers Interval 1598.0 to 2157.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Baseline (B) Egg derived antigen assay	9.65 Titers Interval 8.2 to 11.0	9.92 Titers Interval 8.45 to 12.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (B) egg derived antigen assay	58 Titers Interval 48.0 to 71.0	105 Titers Interval 86.0 to 129.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Baseline(A/H1N1)Cell derived assay	70 Titers Interval 53.0 to 92.0	90 Titers Interval 69.0 to 119.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (A/H1N1) cell derived antigen assay	1076 Titers Interval 886.0 to 1307.0	1296 Titers Interval 1069.0 to 1571.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Baseline(A/H3N2)cell derived assay(N=141,144)	125 Titers Interval 98.0 to 158.0	144 Titers Interval 114.0 to 182.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (A/H3N2) cell derived antigen assay	676 Titers Interval 585.0 to 783.0	1651 Titers Interval 1429.0 to 1908.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Baseline(B)cell derived assay(N=141,144)	22 Titers Interval 18.0 to 27.0	25 Titers Interval 21.0 to 30.0
Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (B) cell derived antigen assay	136 Titers Interval 113.0 to 163.0	186 Titers Interval 155.0 to 222.0

SECONDARY outcome

Timeframe: Day 29 post vaccination

Population: The analysis was performed on the per-protocol dataset.

Immunogenicity was evaluated in terms of Geometric Mean Ratio (GMRs) in 9 to 17 year-old children and adolescents after one injection of either cTIV vaccine or eTIV.

The criterion is met according to European (CHMP) guideline if the mean geometric increase GMR (day29/day1) in HI antibody titer is >2.5.

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=142 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=144 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Day29(B) cell derived antigen assay(N=141,144)	6.15 Ratio Interval 4.96 to 7.63	7.37 Ratio Interval 5.96 to 9.12
Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Day 29 (A/H1N1)egg derived antigen assay	16 Ratio Interval 12.0 to 21.0	14 Ratio Interval 11.0 to 19.0
Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Day 29 (A/H3N2) egg derived antigen assay	5.84 Ratio Interval 4.43 to 7.7	12 Ratio Interval 9.33 to 16.0
Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Day 29 (B) egg derived antigen assay	6.03 Ratio Interval 4.77 to 7.62	11 Ratio Interval 8.43 to 13.0
Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Day29(A/H1N1)cell derived antigen assay(N=141,144)	15 Ratio Interval 12.0 to 21.0	14 Ratio Interval 11.0 to 19.0
Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Day29(A/H3N2)cell derived antigen assay(N=141,144)	5.45 Ratio Interval 4.21 to 7.06	11 Ratio Interval 8.87 to 15.0

SECONDARY outcome

Timeframe: Day 29 post vaccination

Population: The analysis was performed on the per-protocol dataset.

To evaluate immunogenicity in terms of percentage of 9 to 17 year-old children and adolescents achieving HI titers ≥40, after one injection of either the cTIV vaccine or the eTIV vaccine.

This criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is >70% and according to the US (CBER) guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%.

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=142 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=144 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (A/H3N2) cell derived antigen assay	100 Percentages of subjects Interval 97.0 to 100.0	100 Percentages of subjects Interval 97.0 to 100.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Prevaccination (A/H1N1)egg derived antigen assay	65 Percentages of subjects Interval 57.0 to 73.0	75 Percentages of subjects Interval 67.0 to 82.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (A/H1N1) egg derived antigen assay	99 Percentages of subjects Interval 96.0 to 100.0	99 Percentages of subjects Interval 95.0 to 100.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Prevaccination (A/H3N2) egg derived antigen assay	82 Percentages of subjects Interval 74.0 to 88.0	86 Percentages of subjects Interval 79.0 to 91.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (A/H3N2) egg derived antigen assay	100 Percentages of subjects Interval 97.0 to 100.0	100 Percentages of subjects Interval 97.0 to 100.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Prevaccination(B)egg derived antigen assay	17 Percentages of subjects Interval 11.0 to 24.0	13 Percentages of subjects Interval 8.0 to 19.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (B) egg derived antigen assay	75 Percentages of subjects Interval 67.0 to 82.0	84 Percentages of subjects Interval 77.0 to 90.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Prevaccination (H1N1)cell derived assay(N=141,144)	67 Percentages of subjects Interval 59.0 to 75.0	78 Percentages of subjects Interval 71.0 to 85.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (A/H1N1)cell derived antigen assay	99 Percentages of subjects Interval 96.0 to 100.0	98 Percentages of subjects Interval 94.0 to 100.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Prevaccination (H3N2)cell derived assay(N=141,144)	83 Percentages of subjects Interval 76.0 to 89.0	86 Percentages of subjects Interval 79.0 to 91.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Prevaccination (B) cell derived assay(N=141,144)	40 Percentages of subjects Interval 32.0 to 49.0	47 Percentages of subjects Interval 38.0 to 55.0
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (B) cell derived antigen assay	95 Percentages of subjects Interval 90.0 to 98.0	94 Percentages of subjects Interval 89.0 to 98.0

SECONDARY outcome

Timeframe: Day 29 post vaccination

Population: The analysis was performed on the per-protocol dataset.

Seroconversion or significant increase as per CHMP criteria is defined as percentage of subjects with a pre vaccination HI titer <10 to a post vaccination titer ≥40 or a pre vaccination HI titer ≥10 and a ≥4-fold increase in post vaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion or significant increase should be >40%.

According to the CBER criteria, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion/significant increase should be ≥40%.

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=142 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=144 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (A/H3N2) egg derived antigen assay	56 Percentages of subjects Interval 48.0 to 65.0	77 Percentages of subjects Interval 69.0 to 84.0
Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (B) egg derived antigen assay	56 Percentages of subjects Interval 48.0 to 65.0	71 Percentages of subjects Interval 63.0 to 78.0
Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day29(A/H3N2)cell derived antigen assay(N=141,144)	52 Percentages of subjects Interval 44.0 to 61.0	78 Percentages of subjects Interval 70.0 to 84.0
Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day 29 (A/H1N1) egg derived antigen assay	77 Percentages of subjects Interval 70.0 to 84.0	77 Percentages of subjects Interval 69.0 to 84.0
Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day29(A/H1N1)cell derived antigen assay(N=141,144)	74 Percentages of subjects Interval 66.0 to 81.0	74 Percentages of subjects Interval 66.0 to 81.0
Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents Day29(B)cell derived antigen assay (N=141,144)	63 Percentages of subjects Interval 55.0 to 71.0	69 Percentages of subjects Interval 61.0 to 76.0

SECONDARY outcome

Timeframe: Day 29 and Day 50 post vaccination

Population: The analysis was performed on the per-protocol dataset.

To evaluate immunogenicity in terms of Geometric Mean Titers (GMTs) in children 3 to 8 years of age after two doses of either cTIV vaccine or eTIV,administered 4 weeks apart.

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=524 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=513 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day 29 (A/H1N1) cell derived antigen assay	234 Titers Interval 194.0 to 283.0	192 Titers Interval 159.0 to 232.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Baseline (A/H3N2) cell derived antigen assay	75 Titers Interval 64.0 to 88.0	85 Titers Interval 72.0 to 99.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day 29 (A/H3N2) cell derived antigen assay	653 Titers Interval 536.0 to 795.0	1099 Titers Interval 903.0 to 1339.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day50(A/H3N2)cell derived antigen assay(N=522,513)	858 Titers Interval 744.0 to 990.0	1329 Titers Interval 1152.0 to 1533.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Baseline (B) cell derived antigen assay	8.22 Titers Interval 7.59 to 8.9	8.72 Titers Interval 8.05 to 9.45
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day 29 (B) cell derived antigen assay	29 Titers Interval 24.0 to 36.0	36 Titers Interval 30.0 to 44.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day50 (B) cell derived antigen assay(N=522,513)	53 Titers Interval 46.0 to 62.0	62 Titers Interval 53.0 to 72.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Baseline (A/H1N1) egg derived antigen assay	16 Titers Interval 14.0 to 18.0	15 Titers Interval 13.0 to 17.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day29(A/H1N1)egg derived antigen assay(N=515,507)	152 Titers Interval 124.0 to 186.0	157 Titers Interval 128.0 to 192.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day50(A/H1N1)egg derived antigen assay	407 Titers Interval 358.0 to 462.0	477 Titers Interval 419.0 to 542.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Baseline (A/H3N2) egg derived antigen assay	68 Titers Interval 58.0 to 80.0	74 Titers Interval 63.0 to 87.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day29(A/H3N2)egg derived antigen assay(N=515,507)	584 Titers Interval 478.0 to 713.0	1075 Titers Interval 880.0 to 1312.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day50(A/H3N2)egg derived antigen assay	768 Titers Interval 666.0 to 885.0	1293 Titers Interval 1121.0 to 1491.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Baseline (B) egg derived antigen assay	6.16 Titers Interval 5.86 to 6.48	6.24 Titers Interval 5.93 to 6.56
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day29(B) egg derived antigen assay (N=515,507)	19 Titers Interval 16.0 to 22.0	27 Titers Interval 23.0 to 33.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day 50 (B) egg derived antigen assay	25 Titers Interval 21.0 to 29.0	44 Titers Interval 38.0 to 51.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Baseline (A/H1N1) cell derived antigen assay	19 Titers Interval 16.0 to 22.0	17 Titers Interval 14.0 to 19.0
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children Day50(A/H1N1)cell derived antigen assay(N=522,513)	563 Titers Interval 501.0 to 634.0	610 Titers Interval 542.0 to 686.0

SECONDARY outcome

Timeframe: Day 29 and Day 50 post vaccination

Population: The analysis was performed on the per-protocol dataset.

To evaluate immunogenicity in terms of Geometric Mean Ratio (GMR) in children 3 to 8 years of age after two doses of either the cTIV vaccine or the eTIV vaccine, administered 4 weeks apart according to the CHMP criteria.

The criterion is met according to the European (CHMP) guideline if the mean geometric increase (GMR day 29/day 1 and GMR day 50/day 1) in HI antibody titer is >2.5

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=524 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=513 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day29 (A/H1N1)egg derived antigen assay(N=515,507)	9.58 Ratio Interval 8.37 to 11.0	11 Ratio Interval 9.36 to 12.0
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day 50 (A/H1N1) egg derived antigen assay	25 Ratio Interval 23.0 to 28.0	33 Ratio Interval 29.0 to 36.0
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day29 (A/H3N2)egg derived antigen assay(N=515,507)	8.65 Ratio Interval 7.4 to 10.0	15 Ratio Interval 13.0 to 17.0
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day50(A/H1N1)cell derived antigen assay(N=522,513	30 Ratio Interval 27.0 to 34.0	37 Ratio Interval 33.0 to 42.0
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day 29 (A/H3N2) cell derived antigen assay	8.73 Ratio Interval 7.54 to 10.0	13 Ratio Interval 11.0 to 15.0
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day 50 (A/H3N2) egg derived antigen assay	11 Ratio Interval 9.84 to 13.0	17 Ratio Interval 15.0 to 20.0
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day 29 (B) egg derived assay (N=515,507	3.04 Ratio Interval 2.59 to 3.57	4.36 Ratio Interval 3.71 to 5.12
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day 50 (B) egg derived antigen assay	3.99 Ratio Interval 3.49 to 4.57	7.04 Ratio Interval 6.15 to 8.07
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day 29 (A/H1N1) cell derived antigen assay	13 Ratio Interval 11.0 to 14.0	12 Ratio Interval 10.0 to 13.0
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day50(A/H3N2)cell derived antigen assay(N=522,513)	12 Ratio Interval 10.0 to 13.0	16 Ratio Interval 14.0 to 18.0
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day 29 (B) cell derived antigen assay	3.59 Ratio Interval 3.08 to 4.19	4.14 Ratio Interval 3.55 to 4.82
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children Day 50 (B) cell derived antigen assay(N=522,513)	6.5 Ratio Interval 5.75 to 7.34	7.06 Ratio Interval 6.24 to 7.99

SECONDARY outcome

Timeframe: Day 29 and Day 50 post vaccination

Population: The analysis was performed on the per-protocol dataset.

To evaluate immunogenicity in terms of HI titers ≥40, in children 3-8 years of age after two doses of either cTIV vaccine or eTIV vaccine, administered 4 weeks apart.

The criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is >70% and according to the US (CBER) guideline if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%.

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=524 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=513 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day29(A/H1N1)egg derived antigen assay (N=515,507)	72 Percentages of subjects Interval 68.0 to 76.0	68 Percentages of subjects Interval 64.0 to 72.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day29(A/H3N2)egg derived antigen assay(N=515,507)	87 Percentages of subjects Interval 84.0 to 90.0	85 Percentages of subjects Interval 82.0 to 88.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day50 (A/H3N2) egg derived antigen assay	96 Percentages of subjects Interval 94.0 to 98.0	94 Percentages of subjects Interval 91.0 to 96.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Prevaccination (B) egg derived antigen assay	4 Percentages of subjects Interval 3.0 to 7.0	4 Percentages of subjects Interval 3.0 to 6.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day 29 (B) egg derived antigen assay (N=515,507)	35 Percentages of subjects Interval 30.0 to 39.0	40 Percentages of subjects Interval 36.0 to 45.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day 29 (A/H1N1) cell derived antigen assay	82 Percentages of subjects Interval 78.0 to 85.0	76 Percentages of subjects Interval 72.0 to 80.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day 29 (A/H3N2) cell derived antigen assay	89 Percentages of subjects Interval 86.0 to 92.0	85 Percentages of subjects Interval 82.0 to 88.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day50(A/H3N2)cell derived antigen assay(N=522,513)	98 Percentages of subjects Interval 96.0 to 99.0	93 Percentages of subjects Interval 91.0 to 95.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Prevaccination (B) cell derived antigen assay	11 Percentages of subjects Interval 8.0 to 14.0	12 Percentages of subjects Interval 10.0 to 16.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day 50 (B) cell derived antigen assay (N=522,513)	60 Percentages of subjects Interval 56.0 to 65.0	62 Percentages of subjects Interval 57.0 to 66.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Prevaccination (A/H1N1) egg derived antigen assay	35 Percentages of subjects Interval 30.0 to 39.0	31 Percentages of subjects Interval 27.0 to 35.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day 50 (A/H1N1) egg derived antigen assay	96 Percentages of subjects Interval 94.0 to 98.0	97 Percentages of subjects Interval 95.0 to 98.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Prevaccination (A/H3N2) egg derived antigen assay	67 Percentages of subjects Interval 62.0 to 71.0	70 Percentages of subjects Interval 66.0 to 74.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day 50 (B) egg derived antigen assay	40 Percentages of subjects Interval 35.0 to 44.0	55 Percentages of subjects Interval 51.0 to 95.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Prevaccination (A/H1N1) cell derived antigen assay	36 Percentages of subjects Interval 32.0 to 40.0	33 Percentages of subjects Interval 29.0 to 38.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day50(A/H1N1)cell derived antigen assay(N=522,513)	98 Percentages of subjects Interval 97.0 to 99.0	98 Percentages of subjects Interval 96.0 to 99.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Prevaccination (A/H3N2) cell derived antigen assay	71 Percentages of subjects Interval 67.0 to 75.0	75 Percentages of subjects Interval 71.0 to 79.0
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children Day 29 (B) cell derived antigen assay	43 Percentages of subjects Interval 39.0 to 47.0	45 Percentages of subjects Interval 40.0 to 49.0

SECONDARY outcome

Timeframe: Day 29 and Day 50 post vaccination

Population: The analysis was performed on the per-protocol dataset.

Seroconversion or significant increase as per CHMP criteria is defined as percentage of subjects with a pre vaccination HI titer <10 to a post vaccination titer ≥40 or a pre vaccination HI titer ≥10 and a ≥4-fold increase in post vaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion or significant increase should be >40%.

According to the CBER criteria, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion/significant increase should be ≥40%.

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=524 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=513 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day29(A/H3N2) egg derived antigen assay(N=515,507)	65 Percentages of subjects Interval 61.0 to 70.0	78 Percentages of subjects Interval 74.0 to 81.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day29(A/H1N1) egg derived antigen assay(N=515,507)	70 Percentages of subjects Interval 66.0 to 74.0	67 Percentages of subjects Interval 63.0 to 72.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day 50 (H1N1) egg derived antigen assay	94 Percentages of subjects Interval 92.0 to 96.0	96 Percentages of subjects Interval 94.0 to 97.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day 50 (A/H3N2) egg derived antigen assay	77 Percentages of subjects Interval 73.0 to 81.0	86 Percentages of subjects Interval 82.0 to 89.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day29(B) egg derived antigen assay(N=515,507)	33 Percentages of subjects Interval 29.0 to 37.0	38 Percentages of subjects Interval 34.0 to 43.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day 50 (B) egg derived antigen assay	38 Percentages of subjects Interval 34.0 to 42.0	53 Percentages of subjects Interval 49.0 to 58.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day 29 (A/H1N1) cell derived antigen assay	79 Percentages of subjects Interval 75.0 to 83.0	75 Percentages of subjects Interval 70.0 to 78.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day50(A/H1N1)cell derived antigen assay(N=522,513)	96 Percentages of subjects Interval 93.0 to 97.0	96 Percentages of subjects Interval 94.0 to 98.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day 29 (A/H3N2) cell derived antigen assay	70 Percentages of subjects Interval 66.0 to 74.0	76 Percentages of subjects Interval 72.0 to 80.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day50(A/H3N2)cell derived antigen assay(N=522,513)	80 Percentages of subjects Interval 76.0 to 83.0	85 Percentages of subjects Interval 82.0 to 88.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day 29 (B) cell derived antigen assay	40 Percentages of subjects Interval 36.0 to 44.0	41 Percentages of subjects Interval 37.0 to 45.0
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children Day 50(B)cell derived antigen assay(N=522,513)	58 Percentages of subjects Interval 54.0 to 63.0	58 Percentages of subjects Interval 54.0 to 63.0

SECONDARY outcome

Timeframe: up to 7 days after vaccination

Population: The analysis was performed on the safety dataset

To evaluate safety and tolerability in terms of number of 9 to 17 year-old children and adolescents (cohorts 1 and 2) reporting local and systemic reactions following of one injection of the cTIV or the eTIV vaccine .

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=652 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=316 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Injection site induration	44 Subjects	28 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Injection site ecchymosis	34 Subjects	10 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Arthralgia	27 Subjects	17 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Sweating	14 Subjects	3 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Fatigue	57 Subjects	41 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Fever (≥38C) (N=651,316)	5 Subjects	3 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Analgesic Medication Used	42 Subjects	31 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Any Systemic	188 Subjects	95 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Chills	26 Subjects	13 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Malaise	60 Subjects	34 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Myalgia	99 Subjects	59 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Headache	92 Subjects	44 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Any Other	44 Subjects	37 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Any Local	276 Subjects	141 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Injection site pain	220 Subjects	120 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Injection site erythema	91 Subjects	45 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Injection site swelling	32 Subjects	17 Subjects
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. Stayed at home (n=649,316)	9 Subjects	10 Subjects

SECONDARY outcome

Timeframe: up to 7 days after each vaccination

Population: The analysis was performed on the safety dataset set.

To evaluate the safety and tolerability of the cTIV and the eTIV influenza vaccines in 3 to 8 year-old children terms of number of participants reporting local and systemic reactions after each vaccination.

Outcome measures

Measure	Cohort 3 cTIV (3-8 Years) n=1599 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Years) n=1013 Participants All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine.
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Injection site ecchymosis	144 Subjects	99 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Injection site swelling	119 Subjects	85 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Chills	70 Subjects	68 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Malaise	156 Subjects	117 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Arthralgia	65 Subjects	28 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Oral temp; 39 to < 40 C (N=1598,1013)	16 Subjects	15 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Injection site pain	653 Subjects	398 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Injection site erythema	337 Subjects	206 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Injection site induration	141 Subjects	84 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Myalgia	202 Subjects	119 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Headache	182 Subjects	144 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Sweating	47 Subjects	28 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Fatigue	210 Subjects	170 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Fever (≥ 38C)	75 Subjects	60 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Oral temp; 38 to <38.9 C (N=1598,1013)	48 Subjects	43 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Stayed at home (N=1582,1003,1519, 955)	77 Subjects	63 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Analgesic Medication Used	221 Subjects	148 Subjects
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. Oral temp; ≥ 40 C (N=1598,1013)	6 Subjects	1 Subjects

Adverse Events

Cohort 1+2 cTIV (9-17 Years)

Serious events: 5 serious events

Other events: 328 other events

Deaths: 0 deaths

Cohort 1+2 eTIV (9-17 Years)

Serious events: 3 serious events

Other events: 168 other events

Deaths: 0 deaths

Cohort 3 cTIV (3-8 Yrs; 1st Vaccination)

Serious events: 2 serious events

Other events: 799 other events

Deaths: 0 deaths

Cohort 3 eTIV (3-8 Yrs; 1st Vaccination)

Serious events: 0 serious events

Other events: 507 other events

Deaths: 0 deaths

Cohort 3 cTIV (3-8 Yrs; 2nd Vaccination)

Serious events: 7 serious events

Other events: 670 other events

Deaths: 0 deaths

Cohort 3 eTIV (3-8 Yrs; 2nd Vaccination)

Serious events: 5 serious events

Other events: 413 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cohort 1+2 cTIV (9-17 Years) n=652 participants at risk All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine.	Cohort 1+2 eTIV (9-17 Years) n=316 participants at risk All subjects aged 9-17 years received one 0.5 mL injection, of egg -derived trivalent influenza vaccine.	Cohort 3 cTIV (3-8 Yrs; 1st Vaccination) n=1599 participants at risk All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Yrs; 1st Vaccination) n=1013 participants at risk All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine.	Cohort 3 cTIV (3-8 Yrs; 2nd Vaccination) n=1557 participants at risk All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Yrs; 2nd Vaccination) n=977 participants at risk All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine.
Congenital, familial and genetic disorders Thalassemia beta	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.06% 1/1557 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Gastrointestinal disorders Abdominal pain	0.15% 1/652 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Gastrointestinal disorders Appendix disorder	0.15% 1/652 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Abscess limb	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.10% 1/977 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Gastroentritis	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.06% 1/1557 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.10% 1/977 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Infectious mononucleosis	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.06% 1/1599 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Influenza	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.32% 1/316 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Otitis media chronic	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.10% 1/977 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Pelvic abscess	0.15% 1/652 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Pharyngotonsillitis	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.06% 1/1557 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Pneumonia bacterial	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.32% 1/316 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Respiratory tract infection viral	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.06% 1/1557 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Streptococcal bacteraemia	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.32% 1/316 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Infections and infestations Viral infection	0.15% 1/652 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Injury, poisoning and procedural complications Concussion	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.13% 2/1557 • Number of events 2 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Injury, poisoning and procedural complications Contusion	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.06% 1/1599 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.06% 1/1557 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Injury, poisoning and procedural complications Eye injury	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.06% 1/1557 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Nervous system disorders Post procedural haemorrhage	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.10% 1/977 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Investigations Body height below normal	0.15% 1/652 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Metabolism and nutrition disorders Dehydration	0.15% 1/652 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.06% 1/1557 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Psychiatric disorders Major depression	0.15% 1/652 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Reproductive system and breast disorders Ovarian torsion	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.32% 1/316 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/977 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.10% 1/977 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Surgical and medical procedures Tonsillectomy	0.00% 0/652 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/316 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1599 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1013 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.00% 0/1557 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	0.10% 1/977 • Number of events 1 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)

Other adverse events

Measure	Cohort 1+2 cTIV (9-17 Years) n=652 participants at risk All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine.	Cohort 1+2 eTIV (9-17 Years) n=316 participants at risk All subjects aged 9-17 years received one 0.5 mL injection, of egg -derived trivalent influenza vaccine.	Cohort 3 cTIV (3-8 Yrs; 1st Vaccination) n=1599 participants at risk All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Yrs; 1st Vaccination) n=1013 participants at risk All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine.	Cohort 3 cTIV (3-8 Yrs; 2nd Vaccination) n=1557 participants at risk All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine.	Cohort 3 eTIV (3-8 Yrs; 2nd Vaccination) n=977 participants at risk All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine.
General disorders Fatigue	8.7% 57/652 • Number of events 67 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	13.0% 41/316 • Number of events 47 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	9.7% 155/1599 • Number of events 171 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	11.7% 119/1013 • Number of events 143 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	6.4% 99/1557 • Number of events 110 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	8.4% 82/977 • Number of events 92 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
General disorders Injection site erythema	14.0% 91/652 • Number of events 94 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	14.2% 45/316 • Number of events 45 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	12.3% 197/1599 • Number of events 198 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	13.6% 138/1013 • Number of events 139 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	13.4% 209/1557 • Number of events 211 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	12.1% 118/977 • Number of events 121 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
General disorders Injection site induration	6.7% 44/652 • Number of events 44 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	8.9% 28/316 • Number of events 29 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	5.4% 87/1599 • Number of events 89 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	4.3% 44/1013 • Number of events 45 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	4.2% 66/1557 • Number of events 66 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	5.2% 51/977 • Number of events 51 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
General disorders Injection site pain	33.7% 220/652 • Number of events 227 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	38.0% 120/316 • Number of events 122 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	28.2% 451/1599 • Number of events 462 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	24.8% 251/1013 • Number of events 261 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	27.0% 421/1557 • Number of events 430 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	27.2% 266/977 • Number of events 278 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
General disorders Injection site haemorrhage	5.2% 34/652 • Number of events 37 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	3.2% 10/316 • Number of events 11 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	6.1% 98/1599 • Number of events 106 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	5.9% 60/1013 • Number of events 67 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	3.3% 52/1557 • Number of events 58 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	4.4% 43/977 • Number of events 51 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
General disorders Malaise	9.2% 60/652 • Number of events 68 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	10.8% 34/316 • Number of events 41 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	6.4% 103/1599 • Number of events 118 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	7.7% 78/1013 • Number of events 85 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	4.9% 76/1557 • Number of events 86 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	5.1% 50/977 • Number of events 56 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
General disorders Pyrexia	1.8% 12/652 • Number of events 13 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	1.6% 5/316 • Number of events 7 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	5.5% 88/1599 • Number of events 96 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	7.2% 73/1013 • Number of events 84 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	4.0% 63/1557 • Number of events 70 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	4.5% 44/977 • Number of events 49 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Musculoskeletal and connective tissue disorders Myalgia	15.2% 99/652 • Number of events 107 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	18.7% 59/316 • Number of events 67 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	8.8% 141/1599 • Number of events 150 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	7.5% 76/1013 • Number of events 88 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	6.4% 100/1557 • Number of events 103 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	6.9% 67/977 • Number of events 70 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Nervous system disorders Headache	15.2% 99/652 • Number of events 125 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	14.9% 47/316 • Number of events 56 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	8.9% 143/1599 • Number of events 167 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	11.0% 111/1013 • Number of events 135 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	6.0% 94/1557 • Number of events 110 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	7.5% 73/977 • Number of events 89 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)
Respiratory, thoracic and mediastinal disorders Cough	1.5% 10/652 • Number of events 10 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	1.3% 4/316 • Number of events 4 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	7.8% 124/1599 • Number of events 130 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	7.4% 75/1013 • Number of events 87 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	4.5% 70/1557 • Number of events 75 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)	5.2% 51/977 • Number of events 52 • Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1\&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1\&2); day 50 through day 209 (cohort 3)

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: RegistryContactVaccinesUS@novartis.com

Results disclosure agreements

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

Restriction type: GT60