Trial Outcomes & Findings for Evaluating the Infectivity, Safety, and Immunogenicity of Recombinant Live-Attenuated RSV Vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 in RSV-Seronegative Infants 6 to 24 Months of Age (NCT NCT03227029)

Last Updated: 2022-04-22

Results Overview

Solicited adverse events included 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 5 and Table 6 in the protocol document.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

65 participants

Primary outcome timeframe

Measured from Day 0 through Day 28

Results posted on

2022-04-22

Participant Flow

Recruitment period was from September 2017 to October 2019. Participants were recruited from 12 medical clinics all in the United States.

Participant milestones

Participant milestones
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Overall Study STARTED	26	26	13
Overall Study Received Inoculation	26	25	12
Overall Study COMPLETED	22	22	9
Overall Study NOT COMPLETED	4	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Overall Study Child Wheezed (no treatment)	0	1	0
Overall Study No post RSV season visit due to COVID	3	3	2
Overall Study Not able to get to clinic	0	0	1
Overall Study Withdrawal by Subject	1	0	0
Overall Study Unable to receive treatment in time (no treatment)	0	0	1

Baseline Characteristics

Evaluating the Infectivity, Safety, and Immunogenicity of Recombinant Live-Attenuated RSV Vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 in RSV-Seronegative Infants 6 to 24 Months of Age

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=25 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=25 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=12 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops	Total n=62 Participants Total of all reporting groups
Age, Continuous	13 months n=5 Participants	14 months n=7 Participants	9 months n=5 Participants	12.5 months n=4 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	29 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	18 Participants n=7 Participants	3 Participants n=5 Participants	33 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	9 Participants n=7 Participants	3 Participants n=5 Participants	21 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	16 Participants n=7 Participants	9 Participants n=5 Participants	40 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	20 Participants n=4 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	14 Participants n=7 Participants	6 Participants n=5 Participants	35 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	25 participants n=5 Participants	25 participants n=7 Participants	12 participants n=5 Participants	62 participants n=4 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	2.3 Log 2 titers n=4 Participants

PRIMARY outcome

Timeframe: Measured from Day 0 through Day 28

Population: Study participants who received inoculation and were followed on study past Day 0 were included.

Outcome measures

Outcome measures
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=25 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=25 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=12 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Number of Participants With Solicited Adverse Events (AEs) by Grade Otitis Media · Did not have this AE	24 Participants	23 Participants	12 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Lower Respiratory Illness (LRI) with RSV shedding · Grade 2	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade LRI in the absence of RSV shedding · Grade 1	0 Participants	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	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Cough, without LRI · Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Fever · Did not have this AE	21 Participants	22 Participants	11 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Fever · Grade 1	1 Participants	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Fever · Grade 2	1 Participants	2 Participants	1 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Fever · Grade 3	2 Participants	1 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Fever · Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Otitis Media · Grade 1	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Otitis Media · Grade 2	1 Participants	2 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Otitis Media · Grade 3	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Otitis Media · Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Upper Respiratory Illness (URI) · Did not have this AE	9 Participants	7 Participants	7 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Upper Respiratory Illness (URI) · Grade 1	16 Participants	16 Participants	5 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Upper Respiratory Illness (URI) · Grade 2	0 Participants	2 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Upper Respiratory Illness (URI) · Grade 3	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Upper Respiratory Illness (URI) · Grade 4	0 Participants	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	25 Participants	25 Participants	12 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Lower Respiratory Illness (LRI) with RSV shedding · Grade 1	0 Participants	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	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	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade LRI in the absence of RSV shedding · Did not have this AE	25 Participants	25 Participants	12 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade LRI in the absence of RSV shedding · Grade 2	0 Participants	0 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	0 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Cough, without LRI · Did not have this AE	22 Participants	13 Participants	10 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Cough, without LRI · Grade 1	3 Participants	11 Participants	1 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Cough, without LRI · Grade 2	0 Participants	1 Participants	1 Participants
Number of Participants With Solicited Adverse Events (AEs) by Grade Cough, without LRI · Grade 3	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Measured from Day 0 through Day 28

Population: Study participants who received inoculation and were followed on study past Day 0 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 Division of AIDS (DAIDS) AE Grading table v2.0 (see References).

Outcome measures

Outcome measures
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=25 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=25 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=12 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Number of Participants With Unsolicited AEs	9 Participants	13 Participants	5 Participants

PRIMARY outcome

Timeframe: Measured from Day 0 through Day 56

Population: Study participants who received inoculation and were followed on study past Day 0 were included.

A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that: * Results in death during the period of protocol-defined surveillance; * 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; * 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; * Results in a persistent or significant disability/incapacity; * Is a congenital anomaly or birth defect, OR * 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 ΔNS2/Δ1313/I1314L Vaccine n=25 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=25 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=12 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Number of Participants With Serious Adverse Events (SAEs)	0 Participants	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: Study participants who received inoculation and were followed on study past Day 0 were included. One child from a set of twins was randomly selected and excluded from the analysis.

Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes); and/or 2) greater than or equal to 4-fold rise in RSV serum neutralizing antibody titer and/or serum enzyme-linked immunosorbent assay (ELISA) titer to the RSV F protein from study entry to Study Day 56

Outcome measures

Outcome measures
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=25 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=24 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=12 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Number of Participants Infected With RSV Vaccine Virus	22 Participants	23 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 ΔNS2/Δ1313/I1314L Vaccine n=22 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=23 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Peak Titer of Vaccine Virus Shed	3.1 log 10 PFU/mL Interval 1.8 to 3.8	3.2 log 10 PFU/mL Interval 2.8 to 4.0	—

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 with vaccine virus were included.

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

Outcome measures

Outcome measures
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=22 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=23 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Duration of Virus Shedding in Nasal Washes Culture positive	10 days Interval 8.0 to 12.0	10 days Interval 7.0 to 12.0	—
Duration of Virus Shedding in Nasal Washes RT-PCR positive	13 days Interval 12.0 to 16.0	14 days Interval 11.0 to 17.0	—

PRIMARY outcome

Timeframe: Measured at Day 0 and Day 56

Population: Study participants who received inoculation and were followed on study past Day 0 were included. One child from a set of twins was randomly selected and excluded from the analysis.

Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.

Outcome measures

Outcome measures
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=25 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=24 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=12 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titers	15 Participants	22 Participants	0 Participants

PRIMARY outcome

Timeframe: Measured at Day 56

Population: Study participants who received inoculation and were followed on study past Day 0 were included. One child from a set of twins was randomly selected and excluded from the analysis.

Serum RSV-neutralizing antibody titers were assessed by 60% RSV-plaque reduction neutralization titer (RSV-PRNT) assay.

Outcome measures

Outcome measures
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=25 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=24 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=12 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Serum RSV-neutralizing Antibody Titers	5.1 log 2 titers Interval 4.1 to 6.2	6.7 log 2 titers Interval 6.0 to 7.8	2.3 log 2 titers Interval 2.3 to 2.3

PRIMARY outcome

Timeframe: Measured at Day 0 and Day 56

Population: Study participants who received inoculation and were followed on study past Day 0 were included. One child from a set of twins was randomly selected and excluded from the analysis.

Antibodies were assessed by Enzyme-linked Immunosorbent Assay (ELISA). A response was defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.

Outcome measures

Outcome measures
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=25 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=24 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=12 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum Antibody Titers to RSV F Glycoprotein	15 Participants	22 Participants	0 Participants

PRIMARY outcome

Timeframe: Measured at Day 56

Population: Study participants who received inoculation and were followed on study past Day 0 were included. One child from a set of twins was randomly selected and excluded from the analysis.

Serum antibody titers to RSV F glycoprotein were assessed by ELISA.

Outcome measures

Outcome measures
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=25 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=24 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=12 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Serum Antibody Responses to RSV F Glycoprotein	10.4 log 2 titers Interval 9.3 to 11.8	12.6 log 2 titers Interval 11.3 to 13.3	6.4 log 2 titers Interval 4.6 to 7.9

SECONDARY outcome

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

Population: Only participants who had RSV detected in nasal washes or had greater than or equal to 4 fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events were included.

The number of participants who had RSV-associated, symptomatic, medically attended respiratory and febrile illness (MAARI) among those who had indicators of natural infection with wt RSV were presented. Natural infection with wt RSV during the RSV season surveillance was defined as having either RSV detected in nasal washes collected during illness visits for MAARI events or a \> 4-fold rise in serum antibodies from pre- to post-RSV season in the absence of RSV-associated medical events. A participant was only counted once in each MAARI category, and that was 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 5 and Table 6 in the protocol document.

Outcome measures

Outcome measures
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=11 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=5 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=4 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended Fever · No adverse event	9 Participants	4 Participants	4 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended Fever · Grade 1	1 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended Fever · Grade 2	1 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended Fever · Grade 3	0 Participants	1 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended Fever · Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended Otitis Media · No adverse event	9 Participants	4 Participants	3 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended Otitis Media · Grade 1	0 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended Otitis Media · Grade 2	2 Participants	1 Participants	1 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended Otitis Media · Grade 3	0 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended Otitis Media · Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended URI · No adverse event	9 Participants	2 Participants	3 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended URI · Grade 1	0 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended URI · Grade 2	2 Participants	3 Participants	1 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended URI · Grade 3	0 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended URI · Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended LRI · No adverse event	10 Participants	3 Participants	3 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended LRI · Grade 1	0 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended LRI · Grade 2	1 Participants	2 Participants	1 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended LRI · Grade 3	0 Participants	0 Participants	0 Participants
Number of Participants Who Had RSV-associated Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season Medically Attended LRI · Grade 4	0 Participants	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 enrolled 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. One child from a set of twins was randomly selected and excluded from the analysis.

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 subsequent to the time of the inoculation.

Outcome measures

Outcome measures
Measure	RSV ΔNS2/Δ1313/I1314L Vaccine n=11 Participants Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 Vaccine n=4 Participants Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=4 Participants Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Magnitude of Serum RSV-neutralizing Antibody Responses in the Vaccine and Placebo Recipients Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season. Pre-RSV surveillance	4.0 log 2 titers Interval 2.3 to 6.6	6.1 log 2 titers Interval 5.8 to 7.3	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 Experienced Natural Infection With wt RSV During the Subsequent RSV Season. Post-RSV surveillance	10.1 log 2 titers Interval 7.7 to 10.8	10.6 log 2 titers Interval 8.0 to 11.3	5.9 log 2 titers Interval 4.5 to 6.3

Adverse Events

RSV Delta NS2

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

RSV 276

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	RSV Delta NS2 n=25 participants at risk Participants received a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0). RSV ΔNS2/Δ1313/I1314L: 10\^6 plaque-forming units (PFU); administered as nose drops	RSV 276 n=25 participants at risk Participants received a single dose of the RSV 276 vaccine at study entry (Day 0). RSV 276: 10\^5 PFU; administered as nose drops	Placebo n=12 participants at risk Participants received a single dose of placebo at study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
Psychiatric disorders Mental status changes	4.0% 1/25 • 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 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.	0.00% 0/25 • 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 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.	0.00% 0/12 • 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 1 - 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