Trial Outcomes & Findings for Evaluating the Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (RSV LID cp ΔM2-2) in RSV-Seronegative Infants 6 to 24 Months of Age (NCT NCT02890381)

Last Updated: 2021-11-05

Results Overview

Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes) or 2) greater than or equal to 4-fold rise in serum RSV-neutralizing antibody titer between Study Days 0 and 56.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

17 participants

Primary outcome timeframe

Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28 for nasal washes, and at Days 0, 56 for serum RSV-neutralizing antibodies

Results posted on

2021-11-05

Participant Flow

Recruitment period was from September to October 2016. Participants were recruited from medical clinics.

Participant milestones

Participant milestones
Measure	RSV LID cp ΔM2-2 Vaccine Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Overall Study STARTED	11	6
Overall Study COMPLETED	11	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluating the Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (RSV LID cp ΔM2-2) in RSV-Seronegative Infants 6 to 24 Months of Age

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RSV LID cp ΔM2-2 Vaccine n=11 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=6 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops	Total n=17 Participants Total of all reporting groups
Age, Continuous	12 months n=5 Participants	9 months n=7 Participants	10 months n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	11 Participants n=5 Participants	6 Participants n=7 Participants	17 Participants n=5 Participants
Serum RSV-neutralizing antibody titers	2.3 log 2 titers n=5 Participants	2.3 log 2 titers n=7 Participants	2.3 log 2 titers n=5 Participants

PRIMARY outcome

Timeframe: Measured from Day 0 through Day 28

Population: All study participants were included.

Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI). The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 3 and Table 4 in the protocol document.

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=11 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=6 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Number of Participants With Solicited Adverse Events (AEs) by Grade Fever · Did not have this AE	9 Participants	2 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Fever · Grade 1	0 Participants	2 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Fever · Grade 2	1 Participants	1 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Fever · Grade 3	1 Participants	1 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Fever · Grade 4	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Otitis Media · Did not have this AE	8 Participants	6 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Otitis Media · Grade 1	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Otitis Media · Grade 2	3 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Otitis Media · Grade 3	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Otitis Media · Grade 4	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Upper Respiratory Illness (URI) · Did not have this AE	5 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Upper Respiratory Illness (URI) · Grade 1	6 Participants	6 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Upper Respiratory Illness (URI) · Grade 2	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Upper Respiratory Illness (URI) · Grade 3	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Upper Respiratory Illness (URI) · Grade 4	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Lower Respiratory Illness (LRI) with RSV shedding · Did not have this AE	11 Participants	6 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Lower Respiratory Illness (LRI) with RSV shedding · Grade 1	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Lower Respiratory Illness (LRI) with RSV shedding · Grade 2	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Lower Respiratory Illness (LRI) with RSV shedding · Grade 3	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Lower Respiratory Illness (LRI) with RSV shedding · Grade 4	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade LRI in the absence of RSV shedding · Did not have this AE	9 Participants	6 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade LRI in the absence of RSV shedding · Grade 1	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade LRI in the absence of RSV shedding · Grade 2	2 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade LRI in the absence of RSV shedding · Grade 3	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade LRI in the absence of RSV shedding · Grade 4	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Cough, without LRI · Did not have this AE	7 Participants	2 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Cough, without LRI · Grade 1	4 Participants	4 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Cough, without LRI · Grade 2	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Cough, without LRI · Grade 3	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Cough, without LRI · Grade 4	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Measured from Day 0 through Day 28

Population: All participants were included.

Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each unsolicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. AE grading (Grade 1- mild to Grade 4-life-threatening) was done by DAIDS AE Grading table v2.0 (see References).

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=11 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=6 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Number of Participants With Unsolicited AEs by Grade Nasal Congestion · No adverse event	9 Participants	4 Participants
Number of Participants With Unsolicited AEs by Grade Nasal Congestion · Grade 1	2 Participants	2 Participants
Number of Participants With Unsolicited AEs by Grade Nasal Congestion · Grade 2	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Nasal Congestion · Grade 3	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Nasal Congestion · Grade 4	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Discomfort · No adverse event	10 Participants	4 Participants
Number of Participants With Unsolicited AEs by Grade Discomfort · Grade 1	1 Participants	2 Participants
Number of Participants With Unsolicited AEs by Grade Discomfort · Grade 2	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Discomfort · Grade 3	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Discomfort · Grade 4	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Vomiting, Diarrhea, Constipation · No adverse event	9 Participants	5 Participants
Number of Participants With Unsolicited AEs by Grade Vomiting, Diarrhea, Constipation · Grade 1	2 Participants	1 Participants
Number of Participants With Unsolicited AEs by Grade Vomiting, Diarrhea, Constipation · Grade 2	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Vomiting, Diarrhea, Constipation · Grade 3	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Vomiting, Diarrhea, Constipation · Grade 4	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Eczema · No adverse event	11 Participants	5 Participants
Number of Participants With Unsolicited AEs by Grade Eczema · Grade 1	0 Participants	1 Participants
Number of Participants With Unsolicited AEs by Grade Eczema · Grade 2	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Eczema · Grade 3	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Eczema · Grade 4	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Conjunctivitis · No adverse event	10 Participants	6 Participants
Number of Participants With Unsolicited AEs by Grade Conjunctivitis · Grade 1	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Conjunctivitis · Grade 2	1 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Conjunctivitis · Grade 3	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Conjunctivitis · Grade 4	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Irritability · No adverse event	10 Participants	6 Participants
Number of Participants With Unsolicited AEs by Grade Irritability · Grade 1	1 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Irritability · Grade 2	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Irritability · Grade 3	0 Participants	0 Participants
Number of Participants With Unsolicited AEs by Grade Irritability · Grade 4	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Measured from Day 0 through Day 56

Population: All participants were included.

A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that: 1. Results in death during the period of protocol-defined surveillance 2. Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe 3. Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting 4. Results in a persistent or significant disability/incapacity 5. Is a congenital anomaly or birth defect 6. Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=11 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=6 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Number of Participants With Serious Adverse Events (SAEs)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28 for nasal washes, and at Days 0, 56 for serum RSV-neutralizing antibodies

Population: All participants were included.

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=11 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=6 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Number of Participants Infected With RSV Vaccine	6 Participants	0 Participants

PRIMARY outcome

Timeframe: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28

Population: Only participants who met the definition of infection with vaccine virus were included.

This is the highest value per participant of the titer of vaccine virus shed. It was measured by culture. Only participants who met the definition of infection with vaccine virus were included.

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=6 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Peak Titer of Vaccine Virus Shed	1.6 log 10 Plaque Forming Units (PFU)/mL Interval 0.5 to 3.4	—

PRIMARY outcome

Timeframe: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28. Last day positive is reported.

Population: Only participants who met the definition of infection were included.

Determined separately by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=6 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Duration of Virus Shedding in Nasal Washes Culture positive	6 days Interval 0.0 to 12.0	—
Duration of Virus Shedding in Nasal Washes RT-PCR positive	12 days Interval 0.0 to 15.0	—

PRIMARY outcome

Timeframe: Measured at Day 0 and Day 56

Population: One placebo recipient had missing data at the Day 56 evaluation. All other participants were included.

Immunogenicity was assessed pre-inoculation, and at approximately 2 months post-inoculation (Study Day 56). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre and post time points.

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=11 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=5 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titer	5 Participants	2 Participants

PRIMARY outcome

Timeframe: Measured at Day 56

Population: One placebo recipient had missing data at Day 56. All other participants were included.

Immunogenicity was assessed at approximately 2 months post-inoculation (Study Day 56).

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=11 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=5 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Serum Antibody Responses to RSV F Glycoprotein as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)	12.3 log 2 titers Interval 5.7 to 14.2	8.2 log 2 titers Interval 7.1 to 15.2

SECONDARY outcome

Timeframe: Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study

Population: Only participants who had RSV detected in nasal washes or \>=4 fold rise in serum antibodies during the subsequent RSV season were included.

The number of participants who had symptomatic, medically attended respiratory and febrile illness among those who had RSV detected in nasal washes or \>=4 fold rise in serum antibodies during the subsequent RSV season were presented. A participant was only counted once in each solicited AE category, and that was in the line corresponding to the highest grade adverse event they had in that category.

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=3 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=2 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Cough, without LRI · Grade 4	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Fever · Grade 3	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Fever · No adverse event	2 Participants	1 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Fever · Grade 1	1 Participants	1 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Fever · Grade 2	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Fever · Grade 4	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Otitis Media · No adverse event	1 Participants	2 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Otitis Media · Grade 1	1 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Otitis Media · Grade 2	1 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Otitis Media · Grade 3	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Otitis Media · Grade 4	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season URI · No adverse event	1 Participants	2 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season URI · Grade 1	2 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season URI · Grade 2	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season URI · Grade 3	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season URI · Grade 4	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season LRI · No adverse event	0 Participants	1 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season LRI · Grade 1	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season LRI · Grade 2	2 Participants	1 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season LRI · Grade 3	1 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season LRI · Grade 4	0 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Cough, without LRI · No adverse event	0 Participants	1 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Cough, without LRI · Grade 1	1 Participants	0 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Cough, without LRI · Grade 2	2 Participants	1 Participants
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Cough, without LRI · Grade 3	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study

Population: Only participants who had RSV detected in nasal washes or a greater than or equal to 4-fold rise in serum antibodies during the subsequent RSV season were included.

Only participants who had RSV detected in nasal washes or a greater than or equal to 4-fold rise in serum antibodies during the subsequent RSV season were included. RSV-neutralizing antibody titers were measured pre- and post-RSV surveillance season.

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=3 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=2 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Magnitude of Serum RSV-neutralizing Antibody Responses in the Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the Subsequent RSV Season. Pre RSV surveillance	2.3 log 2 titers Interval 2.3 to 3.9	2.3 log 2 titers Interval 2.3 to 2.3
Magnitude of Serum RSV-neutralizing Antibody Responses in the Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the Subsequent RSV Season. Post RSV Surveillance	7.4 log 2 titers Interval 6.5 to 11.0	6.9 log 2 titers Interval 6.8 to 7.0

SECONDARY outcome

Timeframe: Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study

Population: One placebo recipient had missing data for the Day 56 and the pre-RSV surveillance time points. All other participants were included.

A B cell response to vaccine is indicated by a greater than or equal to 4-fold change in serum antibody titers to RSV F glycoprotein between the pre- and post-inoculation time points, and between pre- and post-RSV surveillance time points.

Outcome measures

Outcome measures
Measure	RSV LID cp ΔM2-2 Vaccine n=11 Participants Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=5 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Number of Participants With B Cell Responses to Vaccine From pre- to post-inoculation	5 Participants	2 Participants
Number of Participants With B Cell Responses to Vaccine From pre- to post-RSV surveillance	3 Participants	2 Participants

Adverse Events

Vaccine

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vaccine n=11 participants at risk Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). RSV LID cp ΔM2-2 Vaccine: 10\^5 plaque-forming units (PFUs); administered as nose drops	Placebo n=6 participants at risk Participants received a single dose of placebo at study entry (Day 0). Placebo: Administered as nose drops
Infections and infestations Bronchiolitis	9.1% 1/11 • From study entry to end of study. The duration of follow up for a given participant was between 6 and 10 months depending on time of enrollment. From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1st - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.	0.00% 0/6 • From study entry to end of study. The duration of follow up for a given participant was between 6 and 10 months depending on time of enrollment. From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1st - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
Infections and infestations Bronchitis	9.1% 1/11 • From study entry to end of study. The duration of follow up for a given participant was between 6 and 10 months depending on time of enrollment. From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1st - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.	0.00% 0/6 • From study entry to end of study. The duration of follow up for a given participant was between 6 and 10 months depending on time of enrollment. From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1st - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
Infections and infestations Croup infectious	9.1% 1/11 • From study entry to end of study. The duration of follow up for a given participant was between 6 and 10 months depending on time of enrollment. From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1st - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.	0.00% 0/6 • From study entry to end of study. The duration of follow up for a given participant was between 6 and 10 months depending on time of enrollment. From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1st - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
Infections and infestations Respiratory syncytial virus bronchiolitis	9.1% 1/11 • From study entry to end of study. The duration of follow up for a given participant was between 6 and 10 months depending on time of enrollment. From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1st - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.	0.00% 0/6 • From study entry to end of study. The duration of follow up for a given participant was between 6 and 10 months depending on time of enrollment. From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1st - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
Respiratory, thoracic and mediastinal disorders Wheezing	9.1% 1/11 • From study entry to end of study. The duration of follow up for a given participant was between 6 and 10 months depending on time of enrollment. From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1st - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.	33.3% 2/6 • From study entry to end of study. The duration of follow up for a given participant was between 6 and 10 months depending on time of enrollment. From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1st - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.

Other adverse events

Additional Information

Melissa Allen, Director, IMPAACT Operations Center

Family Health International (FHI 360)

Phone: (919) 405-1429

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place