06 Mat Peds Fleming Dutra 508

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1
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation 
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Evidence to Recommendations Framework Updates
Pfizer Maternal RSVpreF Vaccine
ACIP General Meeting
September 22, 2023Katherine E. Fleming -Dutra, MD
Co-lead, Respiratory Syncytial Virus Vaccines –Pediatric/Maternal Work Group
Coronavirus and Other Respiratory Viruses Division
National Center for Immunization and Respiratory Diseases
2▪Should Pfizer RSVpreF vaccine be recommended for pregnant people to be given 
during 32 through 36 weeks gestation to prevent RSV lower respiratory tract infection 
in infants?Policy question
RSVpreF is a bivalent recombinant stabilized prefusion F protein subunit vaccine.
Key points that have been updated since the June ACIP presentation are highlighted on the slides. 
3▪On August 21, 2023, FDA approved Pfizer RSVpreF vaccine for use in pregnant people 
as a single dose to be given at 32 through 36 weeks gestation
▪In the phase 2b and 3 trials, vaccination was given during 24 through 36 weeks 
gestation 
▪Throughout the presentation, these will be denoted as
•Approved dosing interval (32 –36 weeks gestation)
•Trial dosing interval (24 –36 weeks gestation)FDA approval for RSVpreF vaccine
FDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants | FDA
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
Same Pfizer RSV vaccine, formulation and dose approved for use in adults ages 60 years and older
4Population Pregnant people
Intervention Pfizer RSVpreF vaccine given at 32–36 weeks gestation
Comparison No vaccine
Outcomes▪Medically attended RSV -associated lower respiratory tract infection in infants
▪Hospitalization for RSV -associated lower respiratory tract infection in infants
▪Intensive care unit (ICU) admission from RSV hospitalization in infants
▪Mechanical ventilation from RSV hospitalization in infants
▪RSV -associated death in infants
▪All-cause hospitalization for lower respiratory tract infection in infants
▪All-cause medically attended lower respiratory tract infection in infants
▪Serious adverse events in pregnant people
▪Reactogenicity (grade 3+) in pregnant people
▪Serious adverse events in infants
▪Preterm birth (<37 weeks gestation)Evidence to Recommendations ( EtR ) framework
PICO question
5Evidence to Recommendations ( EtR ) framework
ACIP Evidence to Recommendations Framework (cdc.gov)EtR Domain Question(s)
Public Health Problem ▪Is the problem of public health importance?
Benefits and Harms ▪How substantial are the desirable anticipated effects?
▪How substantial are the undesirable anticipated effects?
▪Do the desirable effects outweigh the undesirable effects?
Values ▪Does the target population feel the desirable effects are large relative 
to the undesirable effects?
▪Is there important uncertainty about, or variability in, how much 
people value the main outcomes?
Acceptability ▪Is the intervention acceptable to key stakeholders?
Feasibility ▪Is the intervention feasible to implement?
Resource Use ▪Is the intervention a reasonable and efficient allocation of resources?
Equity ▪What would be the impact of the intervention on health equity?
6
EtR Domain: Public Health Problem
Is the problem of public health importance?
7▪Most (68%) infants are infected in the first year of life and 
nearly all (97%) by age 2 years2
▪2–3% of young infants will be hospitalized for RSV3,4,5
▪RSV is a common cause of lower respiratory tract infection 
in infants 
▪Highest RSV hospitalization rates occur in first months of 
life and risk declines with increasing age in early 
childhood3,5
▪79% of children hospitalized with RSV aged <2 years had no 
underlying medical conditions3RSV is the leading cause of hospitalization in U.S. 
infants1
1Suh et al. JID 2022 ; 2Glezen et al, Arch Dis Child, 1986 ; 3Hall et al, Pediatrics, 2013 ; 4Langley & Anderson, PIDJ, 2011 ; 5CDC NVSN data
Image: Goncalves et al. Critical Care 
Research and Practice 2012
8▪Is RSV among infants of public health importance? Public Health Problem: Work Group interpretation
NoProbably 
NoProbably 
YesYes VariesDon’t 
know
9
EtR Domain: Benefits and Harms
How substantial are the desirable anticipated effects?
How substantial are the undesirable anticipated effects?
Do the desirable effects outweigh the undesirable 
effects?
10GRADE outcomes, importance, and data sources: Pfizer 
maternal RSVpreF vaccine
RCT = Randomized controlled trial; ICU= intensive care unit
1 Three options: Critical; Important but not critical; Not important for decision making
2 Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial or placebo were inc ludedOutcome Importance1 Data sources
Benefits
Medically attended RSV -associated lower respiratory tract infection in infants Critical Phase 3 RCT
Hospitalization for RSV -associated lower respiratory tract infection in infants Critical Phase 3 RCT
ICU admission from RSV hospitalization in infants Important Phase 3 RCT
Mechanical ventilation from RSV hospitalization in infants Important Phase 3 RCT
RSV -associated death in infants Important Phase 3 and phase 2b2RCT
All-cause medically attended lower respiratory tract infection in infants Important Phase 3 RCT
All-cause hospitalization for lower respiratory tract infection in infants Important Phase 3 RCT
Harms
Serious adverse events in pregnant people Critical Phase 3 and phase 2b2RCT
Reactogenicity (grade 3+) in pregnant people Important Phase 3 and phase 2b2RCT
Serious adverse events in infants Critical Phase 3 and phase 2b2RCT
Preterm birth (<37 weeks gestation) Critical Phase 3 and phase 2b2RCT
11Data available for GRADE and Benefits and Harms
Trial phase Dosing interval Number of Participants* Decision regarding use in GRADE
Phase 2b trial1Trial dosing 
interval (24 –36 
weeks gestation)Vaccine (received phase 3 dose 
and formulation): 115
Placebo: 117Yes. Data for GRADE were limited to participants 
who received placebo or phase 3 vaccine 
formulation and only included for safety 
outcomes. Study was not designed to assess 
efficacy.
Phase 2b trial1Approved dosing 
interval (32 –36 
weeks gestation)Vaccine (received phase 3 dose 
and formulation): 45
Placebo: 44No. Safety data are further limited by small 
sample size. Presented as supplemental data.
Phase 3 trial published 
analyses1,2,3Trial dosing 
interval (24 –36 
weeks gestation)Efficacy set / Safety set
Vaccine: 3495 / 3682
Placebo: 3480 / 3675Yes. Trial was designed and powered using a 24 –
36 weeks dosing interval.
Phase 3 trial, post -hoc 
analysis1Approved dosing 
interval (32 –36 
weeks gestation)Efficacy set / Safety set
Vaccine: 1572 / 1653
Placebo: 1539 / 1632No. Trial was not powered for this interval for 
efficacy, and safety data would be limited in 
power to detect harms. Presented as 
supplemental data.
*For phase 2b trial and phase 3 trial safety set, number of maternal participants are listed. For phase 3 trial efficacy set, number of infants participants are listed.
1 Data provided by Pfizer
2 Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants -PubMed (nih.gov)
3 Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
12Effect estimates and concerns in certainty of assessment, 
benefits : Pfizer maternal RSVpreF vaccine
RCT= randomized controlled trial; CI= confidence interval; ICU= intensive care unit 
1 Three options: Critical; Important but not critical; Not important for decision making
2 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted using the Bonferroni 
procedure and accounting for the primary endpoints results. Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).
3 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered
4 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. Efficacy is from full phase 3 trial data, using trial dosing interval 
(24–36 weeks gestation).
5 Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different p olicy decisions might be considered and fragility of the estimate
6 Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial or placebo were inc ludedOutcome Importance1Data sources Manufacturer 
calculated vaccine efficacyConcerns in certainty 
assessment
Benefits
Medically attended RSV -associated lower respiratory tract infection in 
infants (0 –180 days)Critical Phase 3 RCT 51.3% (97.58% CI: 29.4, 66.8)2 None
Hospitalization for RSV -associated lower respiratory tract infection in 
infants (0 –180 days)Critical Phase 3 RCT 56.8% (99.17% CI: 10.1, 80.7)2 Imprecision (serious)3
ICU admission from RSV hospitalization in infants (0 –180 days) Important Phase 3 RCT 42.9% (95% CI: -124.8, 87.7)4Imprecision (very 
serious)5
Mechanical ventilation from RSV hospitalization in infants (0 –180 days) Important Phase 3 RCT 100% (95% CI: -9.1, 100)4Imprecision (very 
serious)5
RSV -associated death in infants Important Phase 3 and 
phase 2b6RCT1 RSV -associated death occurred in the placebo arm of the 
phase 3 trial that was recorded at day 120 after birth. No RSV -
associated deaths were recorded in the phase 2b trial.
All-cause medically attended lower respiratory tract infection in infants 
(0–180 days)Important Phase 3 RCT 2.5% (99.17% CI: -17.9, 19.4)2 Imprecision (serious)3
All-cause hospitalization for lower respiratory tract infection in infants   
(0–180 days)Important Phase 3 RCT 28.9% (95% CI: -2.0, 50.8)4 Imprecision (serious)3
13Effect estimates and concerns in certainty of assessment, 
harms : Pfizer maternal RSVpreF vaccine
RCT = Randomized -controlled trial
1 Three options: Critical; Important but not critical; Not important for decision making
2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial i nterim analysis, and phase 2b trial among those who received the 
phase 3 vaccine formulation or placebo.
3 Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b RCT did not receive vaccine or placebo i n the approved dosing interval (32 –36 weeks gestation). In the 
approved dosing interval, there is less opportunity for serious adverse events, including preterm birth/delivery, compared to the trial dosing interval (24 –36 weeks gestation).
4 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered
5 Serious concern for indirectness as these data only include systemic reactions. When selecting the a priori harm outcomes, the Work Group defined reactogenicity as both local and systemic 
reactions.
6 Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different p olicy decisions might be considered and not meeting optimal 
information size requirementsOutcome Importance1 Data sources Relative Risk2 (95% 
confidence interval)Concerns in certainty 
assessment
Harms
Serious adverse events in pregnant people Critical Phase 3 and 
phase 2b RCT1.06 (0.95, 1.17) Indirectness (serious)3and
Imprecision (serious)4
Reactogenicity (grade 3+) in pregnant people Important Phase 3 and 
phase 2b RCT0.97 (0.72, 1.31) Indirectness (serious)5
Serious adverse events in infants Critical Phase 3 and 
phase 2b RCT1.01 (0.91, 1.11) Indirectness (serious)3 and 
Imprecision (serious)4
Preterm birth (<37 weeks gestation) Critical Phase 3 and 
phase 2b RCT1.20 (0.99, 1.46) Indirectness (serious)3 and 
Imprecision (very serious)6
14Summary of GRADE: Pfizer maternal RSVpreF vaccine
Outcome Importance Design (# of 
studies)Findings Evidence Type
Benefits
Medically attended RSV -associated lower respiratory 
infection in infants Critical RCT (1) Pfizer RSVpreF maternal vaccine is effective in preventing medically 
attended RSV -associated lower respiratory infection in infants High
Hospitalization for RSV -associated lower respiratory 
tract infection in infants Critical RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing 
hospitalization for RSV -associated lower respiratory tract infection in 
infants Moderate
ICU admission from RSV hospitalization in infants Important RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing ICU 
admission for RSV hospitalization in infantsLow
Mechanical ventilation from RSV hospitalization in 
infants Important RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing 
mechanical ventilation for RSV hospitalization in infantsLow
RSV -associated death in infants Important RCT (2) 1 event observed in a placebo recipient among both trials Not evaluated
All-cause medically attended lower respiratory tract 
infection in infants Important RCT (1) Pfizer RSVpreF maternal vaccine is not effective in preventing all -
cause medically attended lower respiratory tract infection in infants Moderate
All-cause hospitalization for lower respiratory tract 
infection in infants Important RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing all -
cause hospitalization for lower respiratory tract infection in infantsModerate
Harms
Serious adverse events in pregnant people Critical RCT (2) SAEs in pregnant people were balanced between vaccine and placebo 
groupsLow
Reactogenicity (grade 3+) in pregnant people Important RCT (2) Reactogenicity in pregnant people was balanced between vaccine and 
placebo groupsModerate
Serious adverse events in infants Critical RCT (2) SAEs in infants were balanced between vaccine and placebo groups Low
Preterm birth (<37 weeks gestation) Critical RCT (2) Preterm births were unbalanced between vaccine and placebo groups Very low
RCT = Randomized -controlled trial
15Summary of GRADE: Pfizer maternal RSVpreF vaccine
The overall evidence type is driven by the lowest quality of evidence for critical outcomes, and here is driven by the eviden ce rating 
for the critical harm of preterm birth being very low. Overall 
evidence type: 
Very Low

16Effect estimates, benefits : Pfizer maternal RSVpreF vaccine 
comparing trial vs approved dosing interval
CI= confidence interval; ICU=Intensive care unit
1 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. Confidence intervals that are not 95% were adjusted using the Bonferroni 
procedure and accounting for the primary endpoints results. 
2 Vaccine efficacy was calculated as 1 -(hP/[1-P]), where P is the number of cases in the RSVpreF group divided by the total number of cases and h is the ratio of number of participants at risk in the placebo group to 
the number of participants at risk in the RSVpreF group.OutcomeTrial dosing interval
(24–36 weeks gestation)Approved dosing interval 
(32–36 weeks gestation)
Manufacturer calculated  
vaccine efficacy (CI)1Manufacturer calculated vaccine 
efficacy (95% CI)2
Benefits
Medically attended RSV -associated lower respiratory tract 
infection in infants (0 –180 days)51.3% (97.58% CI: 29.4, 66.8) 57.3% (95% CI: 29.8, 74.7)
Hospitalization for RSV -associated lower respiratory tract 
infection in infants (0 –180 days)56.8% (99.17% CI: 10.1, 80.7) 48.2% ( 95% CI: -22.9, 79.6)
ICU admission from RSV hospitalization in infants (0 –180 days)42.9% (95% CI: -124.8, 87.7) 1 event in the vaccine group  
2 events in the placebo group 
Mechanical ventilation from RSV hospitalization in infants (0 –
180 days)100% (95% CI: -9.1, 100) 0 events in the vaccine group  
2 events in the placebo group 
All-cause medically attended lower respiratory tract infection in 
infants (0 –180 days)2.5% (99.17%: -17.9, 19.4) 7.3% ( 95% CI: -15.7, 25.7)
All-cause hospitalization for lower respiratory tract infection in 
infants (0 –180 days)28.9% (95% CI: -2.0, 50.8) 34.7% ( 95% CI: -18.8, 64.9)
17▪As defined in the Pfizer trial, this outcome 
was not included by the Work Group as an 
a priori critical or important outcome for 
GRADE for vaccine policy decisions
▪Severe medically -attended RSV -
associated LRTI* required at least 1 of the 
following signs/ symptoms:
–Fast breathing (respiratory rate ≥70 (<2 month of 
age [60 days]) or ≥60 (≥2 to 12 months of age) 
breaths per minute
–SpO2 measured in room air <93%
–High -flow nasal cannula or mechanical 
ventilation
–ICU admission for >4 hours
–Unresponsive/unconscious▪Included by the Work Group as an a priori
critical outcome for GRADE for vaccine 
policy decisions
▪Medically -attended RSV -associated LRTI* 
required at least 1 of the following 
signs/symptoms:
–Fast breathing: respiratory rate ≥60 (<2 months 
of age [60 days]) or ≥50 (≥2 to 12 months of age) 
breaths per minute
–SpO2 measured in room air <95%
–Chest wall indrawingSevere medically attended RSV -associated lower 
respiratory tract infection (LRTI), co -primary trial endpoint
*Medically attended visit includes inpatient and outpatient encounters. Additionally, definition also required RT -PCR or nucleic acid amplification (NAAT) test positive for RSV. Blue text 
denotes differences between the two definitions. SpO2= Peripheral capillary oxygen saturation
1. Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants -PubMed (nih.gov)
2. Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
18Phase 3 trial vaccine efficacy against severe medically 
attended RSV -associated LRTI, co -primary trial endpoint
1 Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, 99.5% 
confidence intervals (CIs) were used (determined by the alpha -spending function and adjusted with the use of the Bonferroni proc edure), and at later intervals, 97.58% CIs were 
used (based on a two -sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure).
2 Vaccine efficacy was calculated as 1 -(hP/[1-P]), where P is the number of cases in the RSVpreF group divided by the total number of cases and h is the ratio of number of 
participants at risk in the placebo group to the number of participants at risk in the RSVpreF group.
1. Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants -PubMed (nih.gov)
2.Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDATime period 
after birthTrial dosing interval
(24–36 weeks gestation)
Vaccine efficacy1 (99.5% or 
97.58% CI)Approved dosing interval 
(32–36 weeks gestation)
Vaccine efficacy2 
(95% CI)
0–90 days 
after birth81.8% (40.6, 96.3) 91.1% (38.8, 99.8)
0–180 days 
after birth69.4% (44.3, 84.1) 76.5% (41.3, 92.1)Within 0 -180 days after birth
•Among 81 infants with 
severe medically attended 
RSV LRTI, 50 (62%) were 
hospitalized
•Among 63 infants 
hospitalized with RSV, 50 
(79%) had severe medically 
attended RSV LRTI
19Effect estimates, harms : Pfizer maternal RSVpreF vaccine 
comparing trial vs approved dosing interval
CI= confidence interval
1 Phase 3 and 2b trials
2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial i nterim analysis, and phase 2b trial among those who 
received the phase 3 vaccine formulationOutcomeTrial dosing interval1
(24–36 weeks)Approved dosing interval1
(32–36 weeks)
Relative Risk2 (95% CI) Relative Risk2 (95% CI)
Harms
Serious adverse events in pregnant people 1.06 (0.95, 1.17) 1.02 (0.87, 1.20)
Reactogenicity (grade 3+) in pregnant people 0.97 (0.72, 1.31) 0.98 (0.62, 1.54)
Serious adverse events in infants 1.01 (0.91, 1.11) 1.04 (0.90, 1.20)
Preterm birth (<37 weeks gestation) 1.20 (0.99, 1.46) 1.15 (0.82, 1.61)
20Effect estimates, harms : Pfizer maternal RSVpreF vaccine 
comparing trial vs approved dosing interval
CI= confidence interval
1 Phase 3 and 2b trials
2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial i nterim analysis, and phase 2b trial among those who 
received the phase 3 vaccine formulationOutcomeTrial dosing interval1
(24–36 weeks)Approved dosing interval1
(32–36 weeks)
Relative Risk2 (95% CI) Relative Risk2 (95% CI)
Harms
Serious adverse events in pregnant people 1.06 (0.95, 1.17) 1.02 (0.87, 1.20)
Reactogenicity (grade 3+) in pregnant people 0.97 (0.72, 1.31) 0.98 (0.62, 1.54)
Serious adverse events in infants 1.01 (0.91, 1.11) 1.04 (0.90, 1.20)
Preterm birth (<37 weeks gestation) 1.20 (0.99, 1.46) 1.15 (0.82, 1.61)
21▪Trial of a similar GSK maternal RSV vaccine (stabilized prefusion F protein vaccine without an adjuvant) 
was halted due to an imbalance of preterm births with higher numbers in the vaccine vs placebo group
▪Imbalance of neonatal deaths was a consequence of preterm birth imbalance
▪Imbalance in preterm births was seen in low and middle -income countries (RR: 1.57, 95% CI: 1.17, 2.10) 
but not high -income countries (RR: 1.04, 95% CI: 0.68, 1.58)
▪Imbalance was observed from April –December 2021, but not consistently after December 2021  
▪Reason for the imbalance remains unclearGSK maternal RSV vaccine clinical trial and preterm birth
Study vaccine given at 24 0/7 to 34 0/7 weeks gestation
Vaccines and Related Biological Products Advisory Committee February 28 -March 1, 2023 Meeting Briefing Document -Sponsor GSK ( fda.gov)Outcome Vaccine group, n (%) 
N=3,496Placebo group, n (%)
N=1,739Relative Risk (95% CI)
Preterm birth (<37 weeks 
gestation)238 (6.81%) 86 (4.95%) 1.38 (1.08, 1.75)
Neonatal death 13 (0.37%) 3 (0.17%) 2.16 (0.62, 7.55)
22Preterm birth in Pfizer RSVpreF vaccine phase 3 trial data, 
comparing trial vs approved dosing interval
Trial dosing interval
(24–36 weeks gestation)1Approved dosing interval 
(32–36 weeks gestation)1,2
RSVpreF vaccine 
group
N=3,568Placebo group
N=3,558RSVpreF vaccine 
group
N=1,628Placebo group
N=1,604
n % (95% CI) n % (95% CI) n % (95% CI) n % (95% CI)
Preterm birth 
(<37 weeks 
gestation)202 5.7% 
(4.9%, 6.5%)169 4.7% 
(4.1%, 5.5%)68 4.2% 
(3.3%, 5.3%)59 3.7%
(2.8%, 4.7%)
1. Package Insert -ABRYSVO (STN 125768) (fda.gov)
2. Pfizer response to ACIP , unpublished data, August 2023. In package insert, approved dosing interval reported as: 4.2% (68/ 1,631) in the RSVpreF group and 3.7% (59/1,610) in 
the placebo group. 
23Low birth weight and neonatal jaundice outcomes in Pfizer 
RSVpreF vaccine phase 3 trial data, trial vs approved dosing 
interval
Trial dosing interval
(24–36 weeks gestation)1,2Approved dosing interval 
(32–36 weeks gestation) 3
RSVpreF vaccine 
group
N=3,568Placebo group
N=3,558RSVpreF vaccine 
group
N=1,628Placebo group
N=1,604
n % (95% CI) n % (95% CI) n % (95% CI) n % (95% CI)
Low birth 
weight 
(≤2500 g)181 5.1% 
(4.4%, 5.8%)155 4.4%
(3.7%, 5.1%) 67 4.1% 
(3.2%, 5.2%)54 3.4% 
(2.5%, 4.4%)
Neonatal 
jaundice 257 7.2%
(6.4%, 8.1%)240 6.7%
(5.9%, 7.6%)102 6.3%
(5.1%, 7.6%)107 6.7%
(5.5, 8.0%)
1.Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO) (fda.gov)
2.Package Insert -ABRYSVO (STN 125768) (fda.gov)
3.Pfizer response to ACIP , unpublished data, August 2023
24▪Rate of preterm birth by calendar month of birth
▪Birth by week of gestational age
▪Percent of births that were preterm by country
▪Adverse pregnancy outcomesIn June, ACIP requested additional data regarding the 
Pfizer maternal RSV vaccine
25Preterm birth rate for vaccine and placebo recipients by 
calendar time —Pfizer Phase 3 trial, trial dosing interval (24 –
36 weeks gestation)
GSK signal was present from 
April –December 2021
Data source: Pfizer response to ACIP , unpublished data, July 2023
26
Preterm birth rate for vaccine and placebo recipients by 
calendar time —Pfizer Phase 3 trial, approved dosing 
interval (32 –36 weeks gestation)
GSK signal was present from April –
December 2021
Data source: Pfizer response to ACIP , unpublished data, September 2023
27Number of births by gestational age: Pfizer phase 3 trial, 
trial dosing interval (24 –36 weeks gestation)
1 0 1 1 3 1 14 26 291253367641262
738
243
20 1 0 1 0 1 2 3 1 4 2242933497551321
680
251
272 1
0200400600800100012001400
≥27 to <28 weeks
≥28 to <29 weeks
≥29 to <30 weeks
≥30 to <31 weeks
≥31 to <32 weeks
≥32 to <33 weeks
≥33 to <34 weeks
≥34 to <35 weeks
≥35 to <36 weeks
≥36 to <37 weeks
≥37 to <38 weeks
≥38 to <39 weeks
≥39 to <40 weeks
≥40 to <41 weeks
≥41 to <42 weeks
≥42 to <43 weeks
≥43 to <44 weeks
≥44 to <45 weeksNumber of Births
Gestational Age at BirthVaccine Placebo
Preterm birth: <37 weeks gestation
Data source: Pfizer response to ACIP , unpublished data, July 2023
28Number of births by gestational age, preterm births (<37 
weeks gestation) only: Pfizer phase 3 trial, trial dosing 
interval (24 –36 weeks gestation)
1 0 1 1 3 1142629125
1 0 1 2 3 14224293
020406080100120
≥27 to <28 weeks
≥28 to <29 weeks
≥29 to <30 weeks
≥30 to <31 weeks
≥31 to <32 weeks
≥32 to <33 weeks
≥33 to <34 weeks
≥34 to <35 weeks
≥35 to <36 weeks
≥36 to <37 weeksNumber of Births
Gestational Age at BirthVaccine Placebo
Imbalance begins 
at 33 weeks
Preterm birth: <37 weeks gestation
Data source: Pfizer response to ACIP , unpublished data, July 2023
29Number of births by gestational age: Pfizer phase 3 trial, 
approved dosing interval (32 –36 weeks gestation)
Preterm birth: <37 weeks gestation
Data source: Pfizer unpublished data, August 20230 2 6 1149148374567
338
120
121 1 1 51735156334603
325
112
140
0100200300400500600
≥32 to <33 weeks
≥33 to <34 weeks
≥34 to <35 weeks
≥35 to <36 weeks
≥36 to <37 weeks
≥37 to <38 weeks
≥38 to <39 weeks
≥39 to <40 weeks
≥40 to <41 weeks
≥41 to <42 weeks
≥42 to <43 weeks
≥43 to <44 weeksNumber of Births
Gestational Age at BirthVaccine Placebo
30Number of births by gestational age, preterm births (<37 
weeks gestation) only:  Pfizer Phase 3 trial, approved 
dosing interval (32 –36 weeks gestation)
0261149
1 151735
05101520253035404550
≥32 to <33 weeks
≥33 to <34 weeks
≥34 to <35 weeks
≥35 to <36 weeks
≥36 to <37 weeksNumber of Births
Gestational Age at BirthVaccine Placebo
Preterm birth: <37 weeks gestation
Data source: Pfizer unpublished data, August 2023
31Number births and percent preterm by country –Pfizer phase 3 trial
Trial dosing interval (24 –36 weeks gestation) Approved dosing interval (32 –36 weeks gestation)
RSVpreF recipients
N=3568Placebo recipients
N=3558RSVpreF recipients
N=1628Placebo recipients
N=1604
Country No. births % preterm No. births % preterm No. births % preterm No. births % preterm
Argentina 423 6.4% 416 4.1% 230 4.8% 230 4.3%
Australia 11 0.0% 13 7.7% 8 0.0% 8 12.5%
Brazil 35 8.6% 37 2.7% 22 9.1% 23 4.3%
Canada 27 0.0% 28 3.6% 20 0.0% 27 3.7%
Chile 86 8.1% 85 7.1% 47 6.4% 50 2.0%
Denmark 30 3.3% 31 0.0% 21 4.8% 17 0.0%
Finland 75 2.7% 73 1.4% 44 0.0% 40 2.5%
Gambia 78 2.6% 79 2.5% 32 3.1% 24 0.0%
Japan 218 3.2% 216 6.0% 111 2.7% 94 2.1%
Korea 7 0.0% 4 25.0% 6 0.0% 1 100.0%
Mexico 37 8.1% 37 5.4% 13 7.7% 13 0.0%
Netherlands 97 3.1% 95 3.2% 43 2.3% 44 0.0%
New Zealand 49 4.1% 47 6.4% 29 3.4% 28 3.6%
Philippines 32 3.1% 34 5.9% 0 0.0% 1 0.0%
South Africa 469 8.3% 471 4.0% 150 6.7% 127 2.4%
Spain 117 3.4% 123 2.4% 73 2.7% 88 3.4%
Taiwan 123 4.9% 125 5.6% 58 5.2% 57 3.5%
United States 1654 5.7% 1644 5.3% 721 4.0% 732 4.4%
Data source: Pfizer response to ACIP, unpublished data, July and August 2023. Trial included 480 sites across 18 countries. N umb er of births is the total number of births regardless of gestational age. 
Blue indicates higher percent of preterm birth among RSVpreF vs. placebo in trial dosing interval, red in approved dosing int erval, and purple in both dosing intervals. Black indicates either balanced 
preterm birth rates or a higher percent of preterm births among placebo vs RSVpreF recipients. Caution should be used in inte rpreting rates based on small numbers; some differ by very small counts. 
32Number births and percent preterm by country –Pfizer phase 3 trial
Trial dosing interval (24 –36 weeks gestation) Approved dosing interval (32 –36 weeks gestation)
RSVpreF recipients
N=3568Placebo recipients
N=3558RSVpreF recipients
N=1628Placebo recipients
N=1604
Country No. births % preterm No. births % preterm No. births % preterm No. births % preterm
Argentina 423 6.4% 416 4.1% 230 4.8% 230 4.3%
Australia 11 0.0% 13 7.7% 8 0.0% 8 12.5%
Brazil 35 8.6% 37 2.7% 22 9.1% 23 4.3%
Canada 27 0.0% 28 3.6% 20 0.0% 27 3.7%
Chile 86 8.1% 85 7.1% 47 6.4% 50 2.0%
Denmark 30 3.3% 31 0.0% 21 4.8% 17 0.0%
Finland 75 2.7% 73 1.4% 44 0.0% 40 2.5%
Gambia 78 2.6% 79 2.5% 32 3.1% 24 0.0%
Japan 218 3.2% 216 6.0% 111 2.7% 94 2.1%
Korea 7 0.0% 4 25.0% 6 0.0% 1 100.0%
Mexico 37 8.1% 37 5.4% 13 7.7% 13 0.0%
Netherlands 97 3.1% 95 3.2% 43 2.3% 44 0.0%
New Zealand 49 4.1% 47 6.4% 29 3.4% 28 3.6%
Philippines 32 3.1% 34 5.9% 0 0.0% 1 0.0%
South Africa 469 8.3% 471 4.0% 150 6.7% 127 2.4%
Spain 117 3.4% 123 2.4% 73 2.7% 88 3.4%
Taiwan 123 4.9% 125 5.6% 58 5.2% 57 3.5%
United States 1654 5.7% 1644 5.3% 721 4.0% 732 4.4%
Data source: Pfizer response to ACIP, unpublished data, July and August 2023. Trial included 480 sites across 18 countries. N umb er of births is the total number of births regardless of gestational age. 
Blue indicates higher percent of preterm birth among RSVpreF vs. placebo in trial dosing interval, red in approved dosing int erval, and purple in both dosing intervals. Black indicates either balanced 
preterm birth rates or a higher percent of preterm births among placebo vs RSVpreF recipients. Caution should be used in inte rpreting rates based on small numbers; some differ by very small counts. 
33Select pregnancy -related serious adverse events at any 
time following vaccination1,2: Pfizer phase 3 trial, trial 
dosing interval (24 –36 weeks gestation)
1 Table 3 ABRYSVO package insert Package Insert -ABRYSVO (STN 125768) (fda.gov)
2 Includes all SAEs from vaccination to 6 months post -delivery (up to approximately 10 months, depending on the gestational age at the time of vaccination). In the phase 3 RCT, 
eclampsia occurred in 5 participants (3 in the RSVpreF group and 2 in the placebo group) and HELLP syndrome occurred in 5 participants (2 in the RSVpreF group and 3 in the 
placebo group).
3 There was one maternal death in the vaccine group due to postpartum hemorrhage that was not likely to be associated with va ccination.
4 A total of 18 intrauterine deaths were reported for the index pregnancy: 10 intrauterine deaths in the vaccine group (0.3%) and 8 intrauterine deaths in the placebo group 
(0.2%). The intrauterine deaths represented various clinical conditions and presentations resulting in fetal demise without c lear evidence of a common pathophysiology.RSVpreF Vaccine 
N= 3,682Placebo
N= 3,675
Serious Adverse Reaction n (%) 95% CI n (%) 95% CI
All Maternal Serious Adverse Events (SAEs) 598 (16.2) (15.1, 17.5) 558 (15.2) (14.0, 16.4)
Pre-eclampsia 68 (1.8) (1.4, 2.3) 53 (1.4) (1.1, 1.9)
Gestational hypertension 41 (1.1) (0.8, 1.5) 38 (1.0) (0.7, 1.4)
Premature rupture of membranes 15 (0.4) (0.2, 0.7) 16 (0.4) (0.2, 0.7)
Preterm premature rupture of membranes 15 (0.4) (0.2, 0.7) 10 (0.3) (0.1, 0.5)
Hypertension 13 (0.4) (0.2, 0.6) 6 (0.2) (0.1, 0.4)
Maternal death31 (<0.1) (0.0, 0.2) 0 (0.0, 0.1)
Fetal death410 (0.3) (0.1, 0.5) 8 (0.2) (0.1, 0.4)
34▪Same Pfizer RSV vaccine, formulation and dose approved for use in adults ages 60 
years and older
▪Within the trials for this product among adults ages 60 years and older, a potential
safety signal of inflammatory neurologic events was identified
▪A total of 3 cases of interest were recorded among 20,255 investigational vaccine 
recipients aged 60 years and older. No cases were observed among placebo 
recipients.
–1 case of Guillain -Barré Syndrome (GBS)
–1 case of Miller Fisher syndrome (a GBS variant)
–1 case of undifferentiated motor -sensory axonal polyneuropathy (with 
worsening of preexisting symptoms)Other considerations: Inflammatory neurologic events and 
Pfizer RSVpreF Vaccine 
Melgar et al. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immun ization Practices —United States, 2023 | 
MMWR (cdc.gov)
35▪No Guillain -Barré syndrome (GBS) or other demyelinating events were 
reported in the phase 2b or 3 trials among pregnant people1
▪Background rate of GBS in pregnant people is much lower than among 
older adults2,3
▪Incidence rate of GBS in pregnant people in the Vaccine Safety Datalink 
during 2004 –2015 : 2.8 (95% CI 0.5 –9.3) per million person -years (based on 
2 cases)2Other considerations: Inflammatory neurologic events and 
Pfizer RSVpreF Vaccine (cont.)
1.Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
2.Myers TR, McCarthy NL, Panagiotakopoulos L, Omer SB. Estimation of the Incidence of Guillain -Barré Syndrome During Pregnancy in the United States. Open Forum Infect Dis. 
2019 Mar 15;6(3):ofz071. doi: 10.1093/ ofid/ofz071. 
3.Sejvar JJ, Baughman AL, Wise M, Morgan O. Population Incidence of Guillain -Barré Syndrome: A Systematic Review and Meta -Analysis. Neuroepidemiology 2011;36:123 –133 
36▪Efficacious vaccine that can prevent RSV lower respiratory tract 
infection in young infants
▪No consensus among Work Group regarding clinical importance 
of preterm birth imbalance observed in clinical trialsSummary of Benefits and Harms
37▪Though not statistically significant, imbalance in preterm births was seen in the full 
trial population
▪Trial powered for efficacy outcomes and not designed or powered to detect 20% 
increase in preterm birth
▪There may have been less precise dating of gestational age in some sites and 
countries in the trial, but there is no reason this should bias towards a preterm birth 
imbalance among vaccinated compared to placebo participants
▪Preterm birth signal in the GSK maternal RSV vaccine trial (also a stabilized prefusion 
F protein vaccine) adds to concernWork Group members found the following points 
concerning regarding preterm birth
38▪When using the full trial dosing interval (24 –36 weeks gestation), most preterm births (60%) 
were >30 days after vaccination, and no known biologic mechanism for vaccines to cause 
preterm birth, particularly >30 days after vaccination
▪When assessed among those vaccinated during the approved interval (32 –36 weeks 
gestation), data on preterm birth were reassuring to the Work Group
–Imbalance in preterm birth was still present but lessened
–Most infants born preterm in the vaccine group (72%, 49/68) were born at 36 weeks
–In the United States (largest contributing country in the trial), imbalance in preterm births 
reversed: 
•Trial dosing interval: 5.7% in vaccine vs. 5.3% in placebo recipients
•Approved dosing interval: 4.0% in vaccine vs. 4.4% in placebo recipients 
▪Majority of the Work Group felt the approved dosing interval (32 –36 weeks gestation) reduces 
the potential risk of preterm birth and the potential for complications from preterm birth, 
which is their major safety concernWork Group members found the following data reassuring 
regarding preterm birth imbalance
39▪How substantial are the desirable anticipated effects?
–How substantial are the anticipated effects for:
•Medically attended RSV -associated lower respiratory infection in infants 
•Hospitalization for RSV -associated lower respiratory tract infection in infants 
•ICU admission from RSV hospitalization in infants 
•Mechanical ventilation from RSV hospitalization in infants 
•RSV -associated death in infants 
•All-cause hospitalization for lower respiratory tract infection in infants 
•All-cause medically attended lower respiratory tract infection in infants Benefits and Harms -Pfizer maternal RSVpreF vaccine, 
given as a single dose at 32–36 weeks gestation
Minimal Small Moderate Large Varies Don’t know
Minority Opinion Majority Opinion0
40▪How substantial are the undesirable anticipated effects?
–How substantial are the anticipated effects for:
•Serious adverse events in pregnant people 
•Reactogenicity (3+ or higher) in pregnant people 
•Serious adverse events in infants 
•Preterm birth Benefits and Harms -Pfizer maternal RSVpreF vaccine, 
given as a single dose at 32–36 weeks gestation
Minimal Small Moderate Large Varies Don’t know
Majority Opinion
41▪Do the desirable effects outweigh the undesirable effects?
–What is the balance between the desirable effects relative to the 
undesirable effects?Benefits and Harms -Pfizer maternal RSVpreF vaccine, 
given as a single dose at 32–36 weeks gestation
Favors intervention (Pfizer Maternal RSVpreF 
Vaccine)
Favors comparison (No intervention)
Favors both
Favors neither
Unclear0
Majority Opinion
42
EtR Domain: Values
Criterion 1: Does the target population feel that the 
desirable effects are large relative to undesirable effects? 
Criterion 2: Is there important uncertainty about, or 
variability in, how much people value the main 
outcomes?
43▪Values survey of pregnant and recently pregnant people conducted from December 
21, 2022 –January 2, 2023 by University of Iowa, RAND, and CDC1
–68% of respondents had knowledge of RSV prior to taking survey
–61% of respondents said they ‘definitely’ or ‘probably’ would get an RSV vaccine while pregnant
–Among those who did not respond that they “definitely would” get an RSV vaccine while pregnant, safety 
concerns, lack of RSV knowledge, and concerns about vaccination causing or intensifying RSV infection 
were the top reasons for not wanting an RSV vaccine during pregnancy
▪In the US, coverage for recommended vaccines among pregnant people has decreased 
during the pandemic and varies by race and ethnicity2
–Tdap vaccination coverage was 53.5% in 2020 –21 season and 45.8% in 2021 –22 season
–Rates of Tdap coverage were higher in White, non -Hispanic women than among Black, non -Hispanic women 
during the 2020 –21 and 2021 –22 seasonsSummary of values domain
1 CDC and University of Iowa/RAND survey, unpublished
2Flu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC
44▪Criterion 1: Do pregnant people feel that the desirable effects 
are large relative to undesirable effects?Values
No Probably No Probably Yes Yes Varies Don’t know
Majority Opinion
45▪Criterion 2: Is there important uncertainty about, or variability in, 
how much pregnant people value the main outcomes?Values
Important uncertainty or variability
Probably important uncertainty or variability
Probably not important uncertainty or variability
No important uncertainty or variability
No known undesirable outcomes
Most common answers
46
EtR Domain: Acceptability
Is the intervention acceptable to key stakeholders?
47▪Obstetrician and midwife support of RSV vaccine, if it was routinely 
recommended:
–47% definitely
–34% likely
–14% not sure
–4% unlikely
–0.5% very unlikelyMaternity healthcare professionals survey —England, 2019
Wilcox CR, Calvert A, Metz J, et al. Attitudes of Pregnant Women and Healthcare Professionals Toward Clinical Trials and Routine Implementation of Antenatal Vacci nation Against 
Respiratory Syncytial Virus: A Multicenter Questionnaire Study. The Pediatric Infectious Disease Journal. 2019 Sept;38(9):944 -951. DOI: 10.1097/INF.0000000000002384
48▪Is RSV prevention with Pfizer maternal RSVpreF vaccine 
acceptable to key stakeholders?Acceptability
No Probably No Probably Yes Yes Varies Don’t know
Minority Opinion Majority Opinion
49
EtR Domain: Feasibility
Is the intervention feasible to implement?
50▪Storage and handling requirements
–Supplied as single 0.5 mL dose, or as a 5 -pack or 10 -pack of single -dose kits 
–Reconstitution required: single dose vial of lyophilized powder, reconstitution 
supplies included in kit 
–Product should be refrigerated (2 –8°C) in original container, protected from light 
–After reconstitution, the product should be administered within 4 hours, otherwise 
discarded
▪Most pregnant patients receive Tdap vaccine in an obstetrician's or midwife’s office
–Likely pregnant patients would also most often receive RSV vaccine at their prenatal 
care provider’s officeStorage and handling
Package Insert -ABRYSVO (STN 125769/26) (fda.gov) 
Flu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC
51▪Pregnant people may potentially be eligible to receive RSV, Tdap, COVID -19, and 
influenza vaccines at same visit
▪Pfizer Phase 2b study in healthy non -pregnant women ages 18 –49 years on 
simultaneous administration of Tdap and Pfizer RSVpreF found decreased immune 
response to pertussis components (i.e., non -inferiority criteria were not met)1
▪Given lack of correlates of protection for pertussis, it is unclear how this might impact 
protection against pertussis from maternal Tdap when simultaneously administered 
with RSVpreF vaccineSimultaneous administration of RSV vaccine with other 
vaccines in pregnant people
1 Peterson et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When Coadministered With a Tetanus, Diphtheria, and Acellular Pertussis 
Vaccine. The Journal of Infectious Diseases. 2022 June 15; 225(12): 2077 –2086. doi: 10.1093/ infdis /jiab505
52▪Tdap recommended every pregnancy, preferably during the early part of gestational 
weeks 27 through 361
▪Tdap would be preferably given before 32 weeks (based on recommendation) and RSV 
vaccine would be given at or after 32 weeks
▪In MarketScan data from 2018 –2021, about half of captured Tdap doses were given 
before 32 weeks gestation2RSV vaccine and Tdap dosing timing
1 CDC, https://www.cdc.gov/vaccines/vpd/dtap -tdap -td/hcp/recommendations.html
2 MarketScan data, 2018 -2021
53▪Either RSV vaccination during pregnancy or nirsevimab administration for the infant 
can be used to prevent RSV lower respiratory tract infection in infants
▪Work Group felt both products are not needed for most infants
▪Pregnant person and prenatal care provider will need to make the decision during 
pregnancy regarding which RSV prevention product to use
▪Many prenatal care providers may not have time to discuss options for RSV prevention 
with their patients
▪Prenatal care providers may not feel equipped to discuss nirsevimab, as this product 
will be given to the infant after birthRSVpreF vaccine is one of two available preventive 
products for RSV in infants
54▪Maximizes cost -effectiveness
▪Maximizes benefits for infants 
▪Targets dosing to infants who will be in the first months of life during RSV season
▪Another product (nirsevimab) is available for infants who are born out of season —for 
whom maternal vaccine protection would have waned by RSV seasonWork Group unanimously supported use of a seasonal 
dosing strategy for maternal RSV vaccine
55▪Work Group supported seasonal dosing during September through January in most 
of the continental US based on typical (pre -pandemic) RSV seasonality
–Aligns with implementation of influenza vaccine and thus would simplify 
implementation for prenatal care providers 
▪Work Group felt that jurisdictions in which RSV seasonality differs from most of the 
continental US should have flexibility regarding start and stop of administration of 
RSVpreF vaccine in pregnant people
•Alaska
•Tropical climates: parts of Florida, Puerto Rico, U.S. Virgin Islands, Hawaii, Guam, 
and U.S. -affiliated Pacific IslandsSeasonal dosing for RSVpreF vaccine
56▪Is Pfizer Maternal RSVpreF vaccine feasible to implement among 
pregnant people at 32 –36 weeks gestation ?Feasibility
No Probably No Probably Yes Yes Varies Don’t know
Minority Opinion Majority Opinion
57
EtR Domain: Resource Use
Is the intervention a reasonable and efficient allocation of 
resources?
58Scenarios for cost -effectiveness by months of RSVpreF
vaccine dosing during the calendar year
ICER: Incremental cost -effectiveness ratio
QAL Y: Quality -Adjusted Life -Year
Cost -effectiveness model assumes typical RSV seasonality (based on pre -pandemic years) in most of the continental United States.$400,304 
$363,344 
$322,594 
$282,498 
$186,256 $167,280 $141,806 
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000
Base Apr-Feb May-Feb Jun-Feb Aug-Jan Sep-Jan Sep-DecICER ($.QAL Y)
Months of RSV vaccine dosingICER: RSVpreF vs. Natural History
59▪RSVpreF vaccine may improve RSV outcomes but will also increase costs
–Base case incremental cost -effectiveness (ICER) ratio : $400,304/QAL Y
•Year -round dosing 
•Typical RSV seasonality (based on pre -pandemic years) in most of the continental United 
States
–Work group felt that this vaccine would not be cost -effective under the base case conditions
▪Cost -effectiveness would improved by using a seasonal dosing strategy
–September through January in most of the continental US based on typical (pre -pandemic) 
RSV seasonality
▪Work Group unanimously supported use of a seasonal dosing strategyWG interpretations: Resource Use
QAL Y: Quality -Adjusted Life -Year
Cost -effectiveness model assumes typical RSV seasonality (based on pre -pandemic years) in most of the continental United States.
60▪Is Pfizer Maternal RSVpreF vaccine use among pregnant people 
at 32–36 weeks gestation a reasonable and efficient allocation of 
resources?
▪Work Group responses were based on seasonal dosing for RSVpreF vaccine (i.e., 
September -January in most of the continental United States)Resource Use
No Probably No Probably Yes Yes Varies Don’t know
Minority Opinion Majority Opinion
61
EtR Domain: Equity
What would be the impact of the intervention on health equity?
62▪National studies of death certificates found higher rates of RSV -
associated deaths among non -Hispanic Black children compared with 
non -Hispanic White infants and children aged 1 –4 years1
▪ICU admission rates for RSV among Non -Hispanic Black infants <6 
months old were 1.2 –1.6x higher than among Non -Hispanic White infants2
▪RSV hospitalization rates 4 –10x higher among Alaska Native and 
American Indian children ages <24 months than the rate in the general 
population3 
–This study was limited to specific populations and might not be broadly 
representative of risk in all Alaska Native and American Indian childrenEquity summary: Incidence of RSV disease by race and 
ethnicity in infants and children
1. Hansen et al. The Use of Death Certificate Data to Characterize Mortality Associated With Respiratory Syncytial Virus, Unspecified Bronchio litis, and Influenza in the United 
States, 1999 -2018 J Infect Dis. 2022 Aug 15;226(Supplement 2): S255 –S266.
2 Unpublished data from RSV -NET, CDC. 
3 Atwell et al. RSV Among American Indian and Alaska Native Children: 2019 to 2020 Pediatrics. 2023 Aug 1;152(2):e2022060435
63▪By federal law, all states provide Medicaid coverage for pregnancy -related services to 
pregnant women with incomes up to 138% of the federal poverty level1
▪In 2021, 41.0% of mothers had Medicaid at the time of birth2
▪If recommended, ACIP will vote on a Vaccines for Children resolution for the Pfizer 
RSV vaccine for pregnant people <19 years of age
▪After October 1, 2023, when the Inflation Reduction Act provisions become effective, 
state Medicaid agencies will be required to cover vaccines and their administration 
without cost -sharing for nearly all full -benefit adult beneficiaries covered under 
traditional Medicaid, if the CDC/ACIP recommendations applyEquity summary: Medicaid coverage for pregnant people 
and vaccines during pregnancy
1Medicaid Coverage for Women | KFF
2 2023 Medicaid and CHIP Beneficiary Profile: Enrollment, Expenditures, Characteristics, Health Status, and Experience
64▪Under the Affordable Care Act and its implementing regulations, ACIP 
recommendations that have been adopted by CDC “with respect to the individual 
involved” and are “listed on the Immunization Schedules of the Centers for Disease 
Control and Prevention” generally are required to be covered by group health plans 
and health insurance issuers offering group or individual health insurance coverage 
without imposing any cost -sharing requirements (such as a copayment, coinsurance, 
or deductible)Equity summary: Other insurance coverage for vaccines 
during pregnancy
ACIP Shared Clinical Decision -Making Recommendations | CDC
65▪What would be the impact of Pfizer Maternal RSVpreF vaccine 
on health equity?  Answers ranged, no majorityEquity
Reduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t know
2ndmost common Most common 3rd most common
66
Summary
67Evidence to Recommendations ( EtR ) framework
EtR Domain Question(s) Work Group Judgements
Public Health Problem Is the problem of public health importance? Yes
Benefits and Harms How substantial are the desirable anticipated effects? Large
How substantial are the undesirable anticipated effects? Small
Do the desirable effects outweigh the undesirable effects? Favors intervention
Values Does the target population feel the desirable effects are large 
relative to the undesirable effects?Probably yes
Is there important uncertainty about, or variability in, how 
much people value the main outcomes?Probably not important 
uncertainty or variability/ 
Probably important 
uncertainty or variability
Acceptability Is the intervention acceptable to key stakeholders? Yes
Feasibility Is the intervention feasible to implement? Yes
Resource Use Is the intervention a reasonable and efficient allocation of 
resources?Probably yes, with seasonal 
dosing
Equity What would be the impact of the intervention on health 
equity?Ranged from probably no 
impact to increased
68Evidence to Recommendations framework 
Summary: Work Group interpretations
Balance of 
ConsequencesUndesirable
consequences
clearly
outweigh
desirable
consequences
in most 
settingsUndesirable
consequences
probably
outweigh
desirable
consequences
in most settingsThe balance
between
desirable
and 
undesirable
consequences
is closely
balanced or
uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most settingsThere
is insufficient
evidence
to determine
the balance of
consequences
Minority Opinion Majority Opinion
69Evidence to Recommendations framework
Summary: Work Group interpretations
Type of 
RecommendationWe do not 
recommend the 
interventionWe recommend the 
intervention for 
individuals based on 
shared clinical 
decision -makingWe recommend the 
intervention
Minority Opinion Majority Opinion
70▪Majority of Work Group was supportive of intervention with Pfizer maternal RSVpreF 
vaccine for pregnant people with dosing during the approved dosing interval (32 –36 
weeks gestation) 
–Found the data on preterm birth when assessed among those vaccinated during the 
approved dosing interval (32 –36 weeks gestation) to be reassuring 
–Felt the approved dosing interval (32 –36 weeks gestation) reduces the potential risk 
of preterm birth and the potential for complications from preterm birth, which is 
their major safety concern
▪All Work Group members endorsed the importance of post -introduction vaccine safety 
monitoringWork Group considerations: Benefit and harms
71▪Unanimously supported use of a seasonal dosing strategy which would maximize 
benefits and cost -effectiveness 
▪Supported that RSVpreF vaccine dosing should occur during September –January in 
most of the continental United States 
▪Felt that jurisdictions in which RSV seasonality differs from most of the continental US 
should have flexibility regarding start and stop of administration of RSVpreF vaccine in 
pregnant peopleWork Group considerations: Seasonal dosing
72▪Pregnant people should have options for RSV prevention
–Nirsevimab may not be readily available in all settings 
–Pregnant people and their providers may have preferences regarding these two 
products
▪Pregnant people should be made aware that they can either receive RSVpreF vaccine 
during pregnancy or nirsevimab can be given to the infant, but most infants will not 
need both
▪Pregnant people should be informed regarding the risks and benefits of both products 
before making a decisionWork Group considerations: RSVpreF vaccine is one of two 
available preventive products for RSV in infants
73▪Most work group members support a full recommendation
–Approved dosing interval (32 –36 weeks) reduces the potential risk of and complications from preterm birth
–Importance of clear vaccine recommendations
–Providers who will help pregnant people decide which product to receive generally have less familiarity with the 
data than ACIP
–SCDM can be confusing to providers, hard to implement for providers, can lead to lower vaccine confidence and 
uptake of vaccination, and could potentially influence support for the vaccine in lower and middle income 
countries
▪Minority supported a recommendation with SCDM 
–Without SCDM, a full recommendation could result in some providers recommending RSVpreF vaccine during 
pregnancy without discussing with pregnant patients that nirsevimab is an option
–Potential risk for preterm birth (and neuroinflammatory events)
–Same vaccine is recommended under SCDM for adults ages 60 years and older
▪ACIP generally makes SCDM recommendations when individuals may benefit from 
vaccination, but broad vaccination of people in that group is unlikely to have 
population -level impactsWork Group considerations: Full vs shared clinical decision making 
(SCDM) recommendation for Pfizer maternal RSVpreF vaccine during 
the approved dosing interval (32 –36 weeks gestation)
74▪Currently there are no data available on:
–Efficacy of the first lifetime dose during subsequent pregnancies
–Safety of additional doses given in subsequent pregnancies
▪Work Group felt that it was too early to decide whether additional doses should be 
given in subsequent pregnancies given the lack of data
▪Additional data are needed to inform whether additional doses in subsequent 
pregnancies would be indicated, and recommendations can be updated in the futureWork Group considerations: Additional vaccine doses in 
subsequent pregnancies
75▪Maternal RSV vaccine is recommended for pregnant people during 32 
through 36 weeks gestation, using seasonal administration, to prevent 
RSV lower respiratory tract infection in infantsProposed voting language
76Jefferson Jones
Lauren Roper 
Meredith McMorrow 
Mila Prill 
Monica Godfrey 
Michael Melgar
Amadea Britton
Amanda Payne 
Megan Wallace
Danielle Moulia
Morgan Najdowski 
David Hutton Jamison Pike 
Andrew Leidner 
Ismael Ortega -Sanchez 
Karen Broder
Naomi Tepper
Heidi Moline
Amber Winn
Monica Patton
Jenny Milucky
Fiona Havers 
Rebecca Morgan 
Doug Campos -OutcaltPatricia Wodi
Sascha Ellington
Megan Lindley
Fangjun Zhou
Sarah Meyer
David Hutton
Barbara Mahon
Aron Hall
Coronavirus and Other 
Respiratory Viruses Division
Immunization Services 
Division Acknowledgements 
77▪We acknowledge that not every person who can become pregnant identifies as a 
woman. Although we try to use gender -neutral language as often as possible, much of 
the research available currently refers only to “women” when discussing the ability to 
become pregnant. When citing research, we refer to the language used in the study. In 
these cases, “woman” refers to someone who was assigned female at birth. For clarity 
in terminology, “maternal” is used to identify the person who is pregnant or 
postpartum throughout this presentation; the authors are aware that pregnancy is not 
equated with the decision to parent nor do all parents who give birth identify as 
mothers.Note
78
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The findings and conclusions in this report are those of the authors and do not necessarily represent the official 
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation 
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.

79
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation 
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Grading of Recommendations, Assessment, Development, 
and Evaluation (GRADE): 
Pfizer Maternal RSVpreF Vaccine 
Update: September 6, 2023
80Evidence Retrieval, conducted as of April 10, 2023
*Medline (OVID), Embase (OVID), Cochrane Library, CINAHL ( EbscoHost ), Scopus, clinicaltrials.govRecords screened*
(n=161)Duplicates removed
(n=7)
Studies irrelevant
(n=139)Full text studies 
assessed for 
eligibility
(n=12)Studies excluded
(n=10)
7 wrong intervention
3 wrong patient population
Records included 
in evidence 
synthesis 
(n=2)
81▪High certainty: We are very confident that the true effect lies close to that of the 
estimate of the effect.
▪Moderate certainty: We are moderately confident in the effect estimate: The true 
effect is likely to be close to the estimate of the effect, but there is a possibility that it 
is substantially different.
▪Low certainty: Our confidence in the effect estimate is limited: The true effect may be 
substantially different from the effect estimate.
▪Very low certainty: We have very little confidence in the effect estimate: The true 
effect is likely to be substantially different from the estimate of the effect.GRADE Evidence Type
NOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we 
have in the estimates of effect across each outcome.
82▪Initial evidence type (certainty level) determined by study design
–Initial evidence high certainty: A body of evidence from randomized 
controlled trials
–Initial evidence low certainty: A body of evidence from observational 
studies
▪The certainty of evidence may be downgraded due to risk of bias, 
inconsistency, indirectness, imprecision, or publication bias. For non -
randomized studies, the certainty may be rated up for presence of dose -
response gradient, large or very large magnitude of effect, and opposing 
residual confounding.GRADE Evidence Type
NOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we 
have in the estimates of effect across each outcome.
83
Benefits
84Vaccine efficacy methods
*8 participants (3 in the vaccine group and 5 in the placebo group) received injection at >36 weeks gestation and were includ ed in the analysisDosing interval Number of 
ParticipantsVE Formula Outcomes Reference
Phase 3 trial, Trial 
dosing interval 
(24–36 weeks)*Vaccine: 3495
Placebo: 34801–(P/[1 –P]), where P is the number of 
cases in the RSVpreF group divided by 
the total number of cases•Medically attended RSV -associated lower 
respiratory tract infection in infants
•Hospitalization for RSV -associated lower 
respiratory tract infection in infants
•All-cause medically attended lower 
respiratory tract infection in infants Kampmann et al. and 
VRBPAC briefing 
document
Phase 3 trial, Trial 
dosing interval 
(24–36 weeks)*Vaccine: 3495
Placebo: 34801–(P/[1 –P]), where P is the number of 
cases in the RSVpreF group divided by 
the total number of cases•ICU admission from RSV hospitalization in 
infants
•Mechanical ventilation from RSV 
hospitalization in infants
•All-cause hospitalization for lower 
respiratory tract infection in infants Post -hoc analysis, 
data provided by the 
manufacturer for 
GRADE
Phase 3 trial, 
Approved dosing 
interval (32 –36 
weeks) Vaccine: 1572
Placebo: 15391-(hP/[1 -P]), where P is the number of 
cases in the RSVpreF group divided by 
the total number of cases and h is the 
ratio of number of participants at risk in 
the placebo group to the number of 
participants at risk in the RSVpreF groupAll efficacy outcomes Post -hoc analysis, 
data provided by the 
manufacturer
85▪Pfizer phase 3 randomized controlled trial (RCT), MATISSE1
▪Trial locations: Argentina, Australia, Brazil, Canada, Chile, Denmark, Finland, Gambia, Japan, Republic of 
Korea, Mexico, Netherlands, New Zealand, Philippines, South Africa, Spain, Taiwan, United States
–45% of participants from United States
▪Study enrollment and efficacy follow -up occurred June 17, 2020, to October 2, 2022
▪Data evaluated: data cut -off September 30, 2022; mean follow -up in infant participants 11.97 months 
after birth (range: 0.0, 24.3)
▪Infant evaluable efficacy set: 3,495 in vaccine arm; 3,480 in placebo arm
▪Exclusion criteria of certain conditions may not represent all pregnant people and their infants in the 
United States 
▪Placebo was not a saline placebo, but a lyophile match to the vaccine consisting of excipients matched 
to those used in the RSVpreF vaccine formulation, minus the active ingredientsOutcome 1: Medically attended RSV -associated lower 
respiratory tract infection in infants (n=1 study)
1Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480 .
86▪Medically attended visit (inclusive of inpatient and outpatient encounters) 
and ≥1:
–Fast breathing: respiratory rate ≥60 bpm (<2 months of age [60 days]) or 
≥50 bpm (≥2 to 12 months of age)
–SpO2 measured in room air <95%
–Chest wall indrawing
▪RSV RT -PCR –positive test result by Pfizer central laboratory or by 
certified laboratory with NAAT for RSV 
▪Confirmed by endpoint adjudication committee (EAC)Outcome 1: Medically attended RSV -associated lower 
respiratory tract infection in infants (n=1 study)
87Outcome 1: Medically attended RSV -associated lower 
respiratory tract infection in infants (n=1 study)
RR= relative risk, CI=confidence interval
1Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, 99.5% 
confidence intervals (CIs) were used (determined by the alpha -spending function and adjusted with the use of the Bonferroni proc edure), and at later intervals, 97.58% CIs were 
used (based on a two -sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure). Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks 
gestation).
2This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <20%) Time period 
after birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy (1 –RR)
(95% CI)Manufacturer calculated 
vaccine efficacy1 (99.5% 
or 97.58% CI)
0–90 days after 
birth224/3495 56/3480 57.3% (31.3, 73.5) 57.1% (14.7, 79.8)
0–120 days after 
birth35/3495 81/3480 57.0% (36.2, 71.0) 56.8% (31.2, 73.5)
0–150 days after 
birth47/3495 99/3480 52.7% (33.3, 66.5) 52.5% (28.7, 68.9)
0–180 days after 
birth57/3495 117/3480 51.5% (33.7, 64.5) 51.3% (29.4, 66.8)
88▪Medically attended visit (inclusive of inpatient and outpatient encounters) 
and ≥1:
–Fast breathing (respiratory rate ≥70 (<2 month of age [60 days]) or ≥60 (≥2 
to 12 months of age)
–SpO2 measured in room air <93%
–High -flow nasal cannula or mechanical ventilation
–ICU admission for >4 hours
–Unresponsive/unconscious
▪RSV RT -PCR –positive test result by Pfizer central laboratory or by 
certified laboratory with NAAT for RSV 
▪Confirmed by EACOutcome 1: Severe medically attended RSV -associated 
lower respiratory tract infection in infants (n=1 study)
SpO2= Peripheral capillary oxygen saturation; RT -PCR = Real -time polymerase chain reaction; NAAT= nucleic acid amplification technolog y; EAC= endpoint adjudication committee
Blue text denotes differences between definitions of severe medically attended RSV -associated lower respiratory tract infection and medically attended RSV -associated lower 
respiratory tract infection .
89Outcome 1: Severe medically attended RSV -associated 
lower respiratory tract infection in infants (n=1 study)
RR= relative risk, CI= confidence interval
1Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, 99.5% 
confidence intervals (CIs) were used (determined by the alpha -spending function and adjusted with the use of the Bonferroni proc edure), and at later intervals, 97.58% CIs were 
used (based on a two -sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure). 
Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).Time period 
after birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy (1 –RR)
(95% CI)Manufacturer calculated 
vaccine efficacy1 (99.5% or 
97.58% CI)
0–90 days 
after birth6/3495 33/3480 81.9% (56.8, 92.4) 81.8% (40.6, 96.3)
0–120 days 
after birth12/3495 46/3480 74.0% (51.1, 86.2) 73.9% (45.6, 88.8)
0–150 days 
after birth16/3495 55/3480 71.0% (49.6, 83.4) 70.9% (44.5, 85.9)
0–180 days 
after birth19/3495 62/3480 69.5% (49.1, 81.7) 69.4% (44.3, 84.1)
90▪Measures of effect
–Relative Risk: 0.487 (97.58% CI: 0.332, 0.706)
–Absolute Risk1: 1,725 fewer per 100,000 (988 to 2,246 fewer); NNV: 58 (45, 101)
–Absolute Risk2: 11,850 fewer per 100,000 (6,791 to 15,431 fewer); NNV: 8 (6, 15)
–Absolute Risk3: 5,643 fewer per 100,000 (3,234 to 7,348 fewer); NNV: 18 (14, 31)
▪Concerns in certainty assessment: 
–None
▪Evidence type: HighGRADE: Medically attended RSV -associated lower 
respiratory infection in infants (n=1 study)
1Calculated using the observed outcomes in the placebo arm during the clinical trial follow -up (3.4%)
2Calculated using rate from Lively 2019 JPIDS , 2004 -2009 from 3 New Vaccine Surveillance Network (NVSN) sites from Nov -Apr season, included if with acute respiratory infection
(ARI), not restricted to lower respiratory tract infection (LRTI). 
3Calculated assuming 47.5% of ARI from Lively et al paper were LRTI ( Rainisch 2020 Vaccine )
NNV= Number needed to vaccinate
91▪Phase 3 RCT, MATISSE1
▪A respiratory tract infection due to RSV that results in hospitalization
▪Confirmed by endpoint adjudication committee (EAC)Outcome 2: Hospitalization for RSV -associated lower 
respiratory tract infection in infants (n=1 study)
1Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.
92Outcome 2: Hospitalization for RSV -associated lower 
respiratory tract infection in infants (n=1 study)
RR= relative risk, CI= confidence interval
1Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted 
using the Bonferroni procedure and accounting for the primary endpoints results. As a secondary endpoint, the criterion for v accine efficacy was a
lower bound of the confidence interval >0%. 
2This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <0%) 
Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).Time period after 
birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy 
(1 –RR) (95% CI)Manufacturer calculated 
vaccine efficacy1
(99.17% CI)
0–90 days after birth 10/3495 31/3480 67.9% (34.6, 84.2) 67.7% (15.9, 89.5)
0–120 days after birth 15/3495 37/3480 59.6% (26.6, 77.8) 59.5% (8.3, 83.7)
0–150 days after birth 17/3495 39/3480 56.6% (23.4, 75.4) 56.4% (5.2, 81.5)
0–180 days after birth 19/3495 44/3480 57.0% (26.5, 74.8) 56.8% (10.1, 80.7)
0–360 days after 
birth238/3495 57/3480 33.6% (0.2, 55.8) 33.3% ( -17.6, 62.9)
93▪Measures of effect
–Relative risk: 0.432 (99.17% CI: 0.193, 0.899)
–Absolute risk1: 718 fewer per 100,000 (128 to 1,020 fewer); NNV: 139 (98, 781)
–Absolute risk2: 1,051 fewer per 100,000 (187 to 1,493 fewer); NNV: 95 (67, 535)
▪Concerns in certainty assessment: 
–Serious concern for imprecision due to the width of the confidence interval 
containing estimates for which different policy decisions might be considered
▪Evidence type: ModerateGRADE: Hospitalization for RSV -associated lower 
respiratory tract infection in infants (n=1 study)
1Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. 
2Calculated using the rate of acute respiratory infection (ARI) hospitalizations for infants 0 -5 months (2016 -2020 NVSN, unpubli shed)  
94Outcome 3: ICU admission from RSV hospitalization in 
infants (n=1 study)
RR= relative risk, CI= confidence interval
1Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases.
Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).Time period after 
birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy   
(1 –RR) (95% CI)Manufacturer calculated 
vaccine efficacy1(95% CI)
0–90 days after birth 2/3495 6/3480 66.8% ( -64.3, 93.3) 66.7% ( -86.4, 96.7)
0–150 days after 
birth4/3495 6/3480 33.6% ( -135, 81.3) 33.3% ( -181.1, 86.2)
0–180 days after 
birth4/3495 7/3480 43.1% ( -94.2, 83.3) 42.9% ( -124.8, 87.7)
95▪Measures of effect
–Relative risk: 0.571 (95% CI: 0.123, 2.248)
–Absolute risk1: 86 fewer per 100,000 (from 176 fewer to 251 more)
–Absolute risk2: 285 fewer per 100,000 (from 583 fewer to 830 more)
▪Concerns in certainty assessment: 
–Very serious concern for imprecision due to the width of the confidence interval 
containing estimates for which different policy decisions might be considered and 
fragility of the estimate
▪Evidence type: LowOutcome 3: ICU admission from RSV hospitalization in 
infants (n=1 study)
1Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.
2Calculated using the rate of ICU admissions in hospitalizations from Arriola 2019 JPIDS and acute respiratory infection (ARI) hospitalizations for infants 0 -5 months (2016 -2020 
NVSN, unpublished) 
96Outcome 4: Mechanical ventilation1from RSV 
hospitalization in infants (n=1 study)
RR= relative risk, CI= confidence interval
Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation)
1 Invasive or non -invasive mechanical ventilation
2 Using 0.5 offset to account for zero events in the vaccine arm
3 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total numbe r of casesTime period after 
birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy2
(1 –RR) (95% CI)Manufacturer calculated 
vaccine efficacy3 (95% CI)
0–90 days after 
birth0/3495 4/3480 88.9% ( -105.4, 99.4) 100% ( -51.5, 100)
0–150 days after 
birth0/3495 4/3480 88.9% ( -105.4, 99.4) 100% ( -51.5, 100)
0–180 days after 
birth0/3495 5/3480 90.0% ( -63.6, 99.5) 100% ( -9.1, 100)
97▪Measures of effect
–Relative risk: 0.001 (95% CI: 0.001, 1.091)
–Absolute risk1: 144 fewer per 100,000 (144 fewer to 13 more)
–Absolute risk2: 209 fewer per 100,000 (209 fewer to 19 more)
▪Concerns in certainty assessment: 
–Very serious concern for imprecision due to the width of the confidence interval 
containing estimates for which different policy decisions might be considered and 
fragility of the estimate
▪Evidence type: LowOutcome 4: Mechanical ventilation from RSV 
hospitalization in infants (n=1 study)
1Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up
2Calculated using the rate of mechanical ventilations in hospitalizations from Arriola 2019 JPIDS and acute respiratory infect ion (ARI) hospitalizations for infants 0 -5 months (2016 -
2020 NVSN, unpublished)  
98▪Phase 3 RCT, MATISSE and Phase 2b RCT (unpublished, data obtained from 
manufacturer)
▪Phase 2b RCT1,2
–Pregnant people ages 18 –49 in Argentina, Chile, South Africa and United States
•Infant safety set: 114 in vaccine arm (phase 3 formulation); 116 in placebo arm
▪1 RSV -associated death occurred in an infant in the placebo group recorded at day 120 
after birth in the Phase 3 study, no RSV -associated deaths occurred in the RSVpreF 
group
▪No RSV -associated deaths were recorded in the Phase 2b study among those who 
received the phase 3 formulation or placebo
▪Outcome not included in GRADEOutcome 5: RSV -associated death in infants (n=2 studies)
1Simões EAF, Center KJ, Tita ATN, et al. Prefusion F Protein –Based Respiratory Syncytial Virus Immunization in Pregnancy. N Engl J Med. 2022 Apr 28. doi: 
10.1056/NEJMoa2106062.
2https://www.clinicaltrials.gov/ct2/show/study/NCT04032093
99▪Phase 3 RCT, MATISSE1
▪Infant with any medically attended -RTI visit (inpatient or outpatient) AND
–Fast breathing (respiratory rate ≥60 bpm for <2 months of age [<60 days of 
age] or ≥50 bpm for ≥2 to <12 months of age) OR
–SpO2 <95% OR
–Chest wall indrawingOutcome 6: All -cause medically attended lower respiratory 
tract infection in infants (n=1 study)
100Outcome 6: All -cause medically attended lower respiratory 
tract infection in infants (n=1 study)
RR= relative risk, CI= confidence interval
1Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted 
using the Bonferroni procedure and accounting for the primary endpoints results. As a secondary endpoint, the criterion for v accine efficacy was a
lower bound of the confidence interval >0%. Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).
2This outcome did not meet success criterion (lower bound of CI was <0%) Time period 
after birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy 
(1 –RR) (95% CI)Manufacturer calculated 
vaccine efficacy1  (99.17% CI)
0–90 days after 
birth2186/3495 200/3480 7.4% ( -12.4, 23.7) 7.0% ( -22.3, 29.3)
0–120 days after 
birth2261/3495 278/3480 6.5% ( -10, 20.5) 6.1% ( -18.3, 25.5)
0–150 days after 
birth2331/3495 349/3480 5.6% ( -8.9, 18.1) 5.2% ( -16.5, 22.8)
0–180 days 
after birth2392/3495 402/3480 2.9% ( -10.7, 14.8) 2.5% ( -17.9, 19.4)
0–360 days 
after birth2504/3495 531/3480 5.5% ( -5.8, 15.5) 5.1% ( -12.1, 19.6)
101▪Measures of effect
–Relative risk: 0.975 (99.17% CI: 0.806, 1.179)
–Absolute risk*: 289 fewer per 100,000 (2,241 fewer to 2,068 more)
▪Concerns in certainty assessment
–Serious concern for imprecision due to the width of the confidence interval 
containing estimates for which different policy decisions might be considered
▪Evidence type: ModerateGRADE: All -cause medically attended lower respiratory 
tract infection in infants (n=1 study)
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be interpreted in this 
context.
102Outcome 7: All -cause hospitalization for lower respiratory 
tract infection in infants (n=1 study)
RR= relative risk, CI= confidence interval
1 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total numbe r of cases.
Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).Time period 
after birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy 
(1 –RR) (95% CI)Manufacturer calculated 
vaccine efficacy1(95% CI)
0–90 days 
after birth35/3495 55/3480 36.6% (3.4, 58.4) 36.4% (1.0, 59.6)
0–150 days 
after birth47/3495 67/3480 30.2% ( -1.10, 51.8) 29.9% ( -3.4, 52.7)
0–180 days 
after birth54/3495 76/3480 29.3% (0, 49.9) 28.9% ( -2.0, 50.8)
103▪Measures of effect
–Relative risk: 0.711 (95% CI: 0.492, 1.020)
–Absolute risk*: 631 fewer per 100,000 (from 1,109 fewer to 44 more)
▪Concerns in certainty assessment
–Serious concern for imprecision due to the width of the confidence interval 
containing estimates for which different policy decisions might be considered
▪Evidence type: ModerateOutcome 7: All -cause hospitalization for lower respiratory 
tract infection in infants (n=1 study)
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be interpreted in this 
context.
104
Harms
105▪Phase 3 RCT, MATISSE (unpublished, data obtained directly from 
manufacturer)
–Maternal safety set: 3,682 participants in vaccine arm; 3,675 in placebo arm
▪Phase 2b RCT (unpublished, data obtained directly from manufacturer)
–Maternal safety set: 115 participants in vaccine arm (phase 3 formulation); 
117 in placebo arm
▪Follow up times for serious adverse events reported by maternal 
participants were from vaccination through 6 months after delivery 
(Phase 3) or throughout the study (Phase 2b)Outcome 8: Serious adverse events in pregnant people (n=2 
studies)
106Outcome 8: Serious adverse events in pregnant people (n=2 
studies)
CI= confidence interval
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDATrial Events/Vaccine
(n/N)Events/Placebo
(n/N)Relative Risk (95% CI)
Phase 3 598/3682 (16.2%) 558/3675 (15.1%) 1.07 (0.96, 1.19)
Phase 2b 7/115 (6.1%) 14/117 (12.0%) 0.51 (0.21, 1.21)
Serious adverse events in four vaccine recipients (pain in an arm followed by bilateral lower extremity pain, 
premature labor, systemic lupus erythematosus, and eclampsia) and in one placebo recipient (premature placental 
separation) were assessed by the investigator as being related to the injection. Based on review of the event 
narratives and temporal association of these events to vaccination, FDA agreed with the investigator’s 
assessments that there was a reasonable possibility that these events were related to the study intervention.
107▪Measures of effect
–Relative risk: 1.06 (95% CI: 0.95, 1.17)
–Absolute risk*: 905 more per 100,000 (754 fewer to 2,564 more)
▪Concerns in certainty assessment
–Serious concern for imprecision due to the width of the confidence interval 
containing estimates for which different policy decisions might be considered
–Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b 
RCT did not receive vaccine or placebo in the approved dosing interval (32 –36 weeks 
gestation). In the approved dosing interval, there is less opportunity for serious 
adverse events, including preterm birth/delivery, compared to the trial dosing 
interval (24 –36 weeks gestation).
▪Evidence type: LowGRADE: Serious adverse events in pregnant people (n=2 
studies)
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be interpreted in this 
context. CI= confidence interval
108▪Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly 
from manufacturer)
▪Participants reported local and systemic reactions up to 7 days after 
vaccinationOutcome 9: Reactogenicity (grade 3+) in pregnant people 
(n=2 studies)
109Outcome 9: Reactogenicity (grade 3+) in pregnant people 
Trial Outcome Events/Vaccine
(n/N)Events/Placebo
(n/N)Relative Risk (95% CI)
Phase 3 Local events (grade 3+) 11/3663 (0.3%) 0/3639 (0%) 21.86 (1.29, 371.74)
Systemic events (grade 3+) 83/3663 (2.3%) 83/3640 (2.3%) 0.99 (0.74, 1.34)
Phase 2b Local events (grade 3+) 0/114 (0%) 0/117 (0%) 1.03 (0.02, 51.28)*
Systemic events (grade 3+) 2/114 (1.8%) 4/117 (3.4%) 0.51 (0.10, 2.75)
Grade 3: prevents daily routine activity. For redness or swelling is >10 cm. For vomiting, requires intravenous hydration. Fo r 
diarrhea, includes 6 or more loose stools in 24 hours. Grade 4: requires emergency room visit or hospitalization; for redness
included necrosis or exfoliative dermatitis; for swelling included necrosis. 
*Using 0.5 offset to account for zero events
CI= confidence interval
110▪Measures of effect
–Relative risk: 0.97 (95% CI: 0.72, 1.31)
–Absolute risk*:  69 fewer per 100,000 (648 fewer to 718 more)
▪Concerns in certainty assessment: 
–Serious concern for indirectness as this data only includes systemic 
reactions . When selecting the a priori harm outcomes, the Work Group 
defined reactogenicity as both local and systemic reactions.
▪Evidence type: ModerateOutcome 9: Reactogenicity (grade 3+) in pregnant people 
(n=2 studies)
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be interpreted in this 
context. CI= confidence interval
111▪Phase 3 RCT, MATISSE (unpublished, data obtained directly from 
manufacturer)
–Infant safety set: 3,568 in vaccine arm; 3,558 in placebo arm
▪Phase 2b RCT (unpublished, data obtained directly from manufacturer)
–Infant safety set: 114 in vaccine arm (phase 3 formulation); 116 in placebo 
armOutcome 10: Serious adverse events in infants (n=2 studies)
112Outcome 10: Serious adverse events in infants (n=2 studies)
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA, CI= confidence intervalTrial Events/Vaccine
(n/N)Events/Placebo
(n/N)Relative Risk (95% CI)
Phase 3 625/3568 (17.5%) 623/3558 (17.5%) 1.00 (0.90, 1.11)
Phase 2b 41/114 (36.0%) 38/116 (32.8%) 1.10 (0.77, 1.57)
No serious adverse events in infants were considered by the investigators to be related to the vaccine. For infant deaths in the
RSVpreF group, the FDA agreed with the investigator’s conclusions for 4 out of 5 of the infant deaths; however, for 1 case of
extreme prematurity in an infant born to an 18 -year -old mother at 10 days after vaccination who died from prematurity -related 
complications, FDA was unable to exclude the possibility of the extreme prematurity and subsequent death being related to 
receipt of the investigational product. No non -fatal SAEs in infant participants were considered related to maternal vaccination by 
FDA.
113▪Measures of effect
–Relative risk: 1.01 (95% CI: 0.91, 1.11)
–Absolute risk*:  180 more per 100,000 (1,619 fewer to 1,979 more)
▪Concerns in certainty assessment
–Serious concern for imprecision due to the width of the confidence interval 
containing estimates for which different policy decisions might be considered
–Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b 
RCT did not receive vaccine or placebo in the approved dosing interval (32 –36 weeks 
gestation). In the approved dosing interval, there is less opportunity for serious 
adverse events, including preterm birth/delivery, compared to the trial dosing 
interval (24 –36 weeks gestation)
▪Evidence type: LowGRADE: Serious adverse events in infants (n=2 studies)
CI= confidence interval
114▪Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly 
from manufacturer)
–Gestational age at birth <37 weeks and <34 weeksOutcome 11: Preterm births (n=2 studies)
115
Outcome: Preterm births (n=2 studies), Pfizer maternal 
RSVpreF vaccine
*When reported as an adverse event of special interest, 202 preterm births occurred in the vaccine arm; the relative risk is minimally changed at 1.19 (0.98, 1.45) when using this 
count
**Using 0.5 offset to account for zero events in the vaccine arm
CI= confidence intervalPublication Definition Events/Vaccine
(n/N)Events/Placebo
(n/N)Relative Risk (95% CI)
Phase 3<34 weeks 21/3568 12/3558 1.75 (0.86, 3.54)
<37 weeks 201*/3568 169/3558 1.19 (0.97, 1.45)
Phase 2b<34 weeks 0/115 1/117 0.34 (0.01, 8.24)**
<37 weeks 6/115 3/117 2.03 (0.52, 7.94)
116▪Measures of effect
–Relative risk: 1.20 (0.99, 1.46)
–Absolute risk*:  936 more per 100,000 (from 47 fewer to 2,153 more)
▪Concerns in certainty assessment:
–Very se rious concern for imprecision due to the width of the confidence interval 
containing estimates for which different policy decisions might be considered and 
not meeting optimal information size requirements
–Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b 
RCT did not receive vaccine or placebo in the approved dosing interval (32 –36 weeks 
gestation). In the approved dosing interval, there is less opportunity for serious 
adverse events, including preterm birth/delivery, compared to the trial dosing 
interval (24 –36 weeks gestation)
▪Evidence type: Very lowOutcome: Preterm births (n=2 studies)
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be interpreted in this 
context. CI= confidence interval
117
GRADE additional slides
118Inclusion/exclusion criteria for pregnant people -Phase 3 Trial
Inclusion Exclusion
Healthy women ≤49 years of age who are 
between 24 0/7 and 36 0/7 weeks of gestation on 
the day of planned vaccination, with an 
uncomplicated, singleton pregnancy, who are at 
no known increased risk for complications.
Willing and able to comply with scheduled 
visits, treatment plan, laboratory tests, and 
other study procedures.
Receiving prenatal standard of care based on 
country requirements.
Had a fetal anomaly ultrasound examination 
performed at ≥18 weeks of pregnancy with no 
significant fetal abnormalities observed.
Determined by medical history, physical 
examination, and clinical judgment to be 
appropriate for inclusion in the study.
Documented negative HIV antibody test, 
syphilis test, and hepatitis B virus (HBV) surface 
antigen test during this pregnancy and prior to 
randomization (Visit 1).
Intention to deliver at a hospital or birthing 
facility where study procedures can be 
obtained.
Expected to be available for the duration of the 
study and can be contacted by telephone during 
study participation.
Participant is willing to give informed consent 
for her infant to participate in the study.
Capable of giving signed informed consent 
which includes compliance with the 
requirements and restrictions listed in the 
informed consent document (ICD) and in this 
protocol OR If the maternal participant is 
illiterate, a thumbprinted informed consent 
must be obtained, which must be signed and 
dated by an impartial witness who was present 
throughout the entire informed consent process 
confirming that the maternal participant has 
been informed of all pertinent aspects of the 
study.Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not available, the BMI at the time of the first obstetric visit during the current pregnancy may be used.
Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindi cate intramuscular injection.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any compo nen t of the investigational product or any related vaccine.
Current pregnancy resulting from in vitro fertilization.
Current pregnancy complications or abnormalities at the time of consent that will increase the risk associated with the parti cipation in and completion of the study, including but not 
limited to the following:
Preeclampsia, eclampsia, or uncontrolled gestational hypertension.
Placental abnormality.
Polyhydramnios or oligohydramnios.
Significant bleeding or blood clotting disorder.
Endocrine disorders, including untreated hyperthyroidism or untreated hypothyroidism. This also includes disorders of glucose intolerance (e.g., diabetes mellitus type 1 or 2) antedating 
pregnancy or occurring during pregnancy if uncontrolled at the time of consent.
Any signs of premature labor with the current pregnancy or having ongoing intervention (medical/surgical) in the current preg nan cy to prevent preterm birth.
Prior pregnancy complications or abnormalities at the time of consent, based on the investigator's judgment, that will increa se the risk associated with the participation in and completion 
of the study, including but not limited to the following:
Prior preterm delivery ≤34 weeks' gestation.
Prior stillbirth or neonatal death.
Previous infant with a known genetic disorder or significant congenital anomaly.
Major illness of the maternal participant or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with the maternal or infant participant's 
participation in, and completion of, the study or could preclude the evaluation of the maternal participant's response (inclu des positive serologic testing for regional endemic conditions 
assessed during routine maternal care, as per local standards of care and obstetric recommendations).
Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications, including 
monoclonal antibodies, within the year prior to enrollment.
Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation o r behavior or laboratory abnormality that may increase the risk 
associated with study participation or investigational product administration or may interfere with the interpretation of stu dy results and, in the judgment of the investigator, would make 
the participant inappropriate for entry into this study.
Participation in other studies involving investigational drug(s) within 28 days prior to consent and/or during study particip ation.
Receipt of monoclonal antibodies within the year prior to enrollment or the use of systemic corticosteroids for >14 days with in 28 days prior to study enrollment. Permitted treatments 
include the receipt of severe acute respiratory syndrome coronavirus 2 (SARS -CoV -2) monoclonal antibodies, prednisone doses of < 20 mg/day for ≤14 days and, inhaled/nebulized, intra -
articular, intrabursal , or topical (skin or eyes) corticosteroids.
Current alcohol abuse or illicit drug use. Note: Marijuana use is not considered an exclusion criterion for the study when el icited in participant screening, though it may be considered illicit 
in some locales.
Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before investigational product administration, or pl ann ed receipt through delivery, with 1 exception, Rho(D) 
immune globulin (e.g., RhoGAM), which can be given at any time.
Previous vaccination with any licensed or investigational RSV vaccine or planned. Note: Licensed COVID -19 vaccines or COVID -19 v accines authorized for temporary or emergency use will 
not be prohibited during the course of this study.
Investigator site staff members directly involved in the conduct of the study and their family members, site staff members ot herwise supervised by the investigator, or Pfizer employees, 
including their family members, directly involved in the conduct of the study.
Participants who are breastfeeding at the time of enrollment.
119Inclusion/exclusion criteria for infants -Phase 3 Trial
Inclusion Exclusion
Evidence of a signed and dated informed consent document signed by 
the parent(s)/legal guardian(s) OR If the infant participant's maternal 
participant/parent(s)/legal guardian(s) is illiterate, a thumbprinted
informed consent must have been obtained, which must have been 
signed and dated by an impartial witness who was present throughout the 
entire informed consent process confirming that the maternal 
participant/parent(s)/legal guardian(s) has been informed of all pertinent 
aspects of the study for herself (maternal participant) and her fetus/infant 
prior to taking part in the study.
Parent(s)/legal guardian(s) willing and able to comply with scheduled 
visits, treatment plan, laboratory tests, and other study procedures.Infant who is a direct descendant (e.g., child or 
grandchild) of the study personnel.
120Inclusion/exclusion criteria for pregnant people -Phase 2b
Inclusion -Pregnant people Exclusion -Pregnant people
Healthy women 18 to 49 years of age between 24 
and 36 weeks of gestation on the day of planned 
vaccination, with an uncomplicated pregnancy, who 
are at no known increased risk for complications, and 
whose fetus has no significant abnormalities 
observed on ultrasound.
Willing and able to comply with scheduled visits, 
treatment plan, laboratory tests, and other study 
procedures.
Receiving prenatal standard of care.
Had an ultrasound performed at >=18 weeks of 
pregnancy.
Had a negative urinalysis for protein and glucose at 
the screening visit. Trace protein in the urine is 
acceptable if the blood pressure is also normal.
Determined by medical history, physical 
examination, screening laboratory assessment, and 
clinical judgment to be appropriate for inclusion in 
the study.
Documented negative human immunodeficiency 
virus antibody, hepatitis B virus surface antigen, 
hepatitis C virus antibody, and syphilis tests at the 
screening visit.
Body mass index of </=40 kg/m2 at the time of the 
screening visit.
Capable of giving signed informed consent, which 
includes compliance with the requirements and 
restrictions listed in the informed consent document 
and in this protocol.
Expected to be available for the duration of the 
study and willing to give informed consent for her 
infant to participate in the study.Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindi cate 
intramuscular injection.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction to any component of the investig ational product 
or any related vaccine.
History of latex allergy.
History of any severe allergic reaction.
Participants with known or suspected immunodeficiency.
Current pregnancy resulting from in vitro fertilization or other assisted reproductive technology.
A prior history of or known current pregnancy complications or abnormalities that will increase the risk associated with the participant's 
participation in and completion of the study.
Major illness of the mother or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with 
the participant's participation in, and completion of, the study or could preclude the evaluation of the participant's respon se.
Participant with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention including but not 
limited to systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain -Barré syndrome, multip le 
sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis 
(temporal arteritis), psoriasis, and insulin -dependent diabetes mellitus (type 1).
Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation o r behavior or 
laboratory abnormality that may increase the risk associated with study participation or investigational product administrati on or may 
interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inapp ropriate for 
entry into this study.
Participation in other studies involving investigational drug(s) within 28 days prior to study entry and/or during study part icipation.
Participants who receive treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (suc h as for 
cancer or an autoimmune disease), or planned receipt of such treatment or agents during study participation. If systemic cort icosteroids 
have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until 
corticosteroid therapy has been discontinued for at least 30 days before investigational product administration. Inhaled/nebu lized, intra 
articular, intrabursal , or topical (skin or eyes) corticosteroids are permitted.
Current alcohol abuse or illicit drug use.
Receipt of blood or plasma products or immunoglobulin, from 60 days before investigational product administration, or planned receipt 
through delivery, with 1 exception, Rho(D) immune globulin ( eg, RhoGAM), which can be given at any time.
Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.
Laboratory test results at the screening visit outside the normal reference value for pregnant women according to their trime ster in 
pregnancy.
Participants who are breastfeeding at the time of the screening visit.
121Inclusion/exclusion criteria for infants -Phase 2b
Inclusion -Infants Exclusion -Infants
Evidence of a signed and dated informed consent document 
signed by the parent(s).
Parent(s) willing and able to comply with scheduled visits, 
treatment plan, laboratory tests, and other study procedures.Infant who is a direct descendant ( eg, child or grandchild) of the 
study personnel.
122
Figure 1. Enrollment, 
Randomization, 
Administration of Vaccine or 
Placebo, and Follow -up
Kampmann B, Madhi SA, Munjal I, et al. 
Bivalent Prefusion F Vaccine in 
Pregnancy to Prevent RSV Illness in 
Infants. N Engl J Med. 2023 Apr 5. doi: 
10.1056/NEJMoa2216480.
123
Table 1. Demographics of phase 3 trial
Kampmann B, Madhi SA, Munjal I, et al. 
Bivalent Prefusion F Vaccine in Pregnancy to 
Prevent RSV Illness in Infants. N Engl J Med. 
2023 Apr 5. doi: 10.1056/NEJMoa2216480.
124Severity scale for local reactions and systemic events 
(maternal participants)
Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.

125Studies Included in the Review of Evidence
Last name first 
author, Publication 
yearStudy 
designCountry Age 
mean 
(SD), 
yearsTotal Population N intervention N comparison Outcomes Funding 
Source
Kampmann B, 
etal.plus unpublished 
data obtained directly 
from the manufacturer RCT Argentina, Australia, 
Brazil, Canada, Chile, 
Denmark, Finland, 
Gambia, Japan, 
Republic of Korea, 
Mexico, Netherlands, 
New Zealand, 
Philippines, South 
Africa, Spain, Taiwan, 
United States29.0 
(5.7)7,357 3,682 3,675 Medically attended 
RSV -associated lower 
respiratory infection in 
infants; Hospitalization 
for RSV -associated 
lower respiratory tract 
infection in infants; 
RSV -associated death 
in infants; All cause 
medically attended 
lower respiratory tract 
infection in infants; 
Serious adverse events 
in pregnant people; 
Reactogenicity in 
pregnant people; 
Serious adverse events 
in infants; Preterm 
birthPfizer
Pfizer, Phase 2 Trial 
plus unpublished data 
obtained directly from 
the manufacturer RCT Argentina, Chile, 
South Africa and the 
United States27.1
(5.2)232 115 (phase 3 
formulation)117 RSV -associated death 
in infants; Serious 
adverse events in 
pregnant people; 
Reactogenicity in 
pregnant people;
Serious adverse events 
in infants; Preterm 
birth;Pfizer
126Summary of Studies Reporting Outcome 1: Medically 
attended RSV -associated lower respiratory infection in 
infants 
Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be 
interpreted in this context.Last name 
first author, 
Publication 
yearAge 
mean 
(SD), 
yearsN 
interventionN 
comparisonComparator 
VaccineAbsolute 
difference/effect 
estimate 
(97.58% CI)Study 
limitations 
(Risk of Bias)
Kampmann B, 
et al.29.0
(5.7)3495 3480 Placebo 1,725 fewer per 
100,000 (988 to 
2,246 fewer)None
127Summary of Studies Reporting Outcome 2: 
Hospitalization for RSV -associated lower respiratory 
tract infection in infants 
Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be 
interpreted in this context.Last name first 
author, 
Publication 
yearAge 
mean 
(SD), 
yearsN 
interventio
nN 
comparisonComparato
r VaccineAbsolute 
difference/effect 
estimate 
(99.17% CI)Study 
limitations 
(Risk of Bias)
Kampmann B, 
et al.29.0 
(5.7)3495 3480 Placebo 718 fewer per 
100,000 (128 to 
1,020 fewer)None
128Summary of Studies Reporting Outcome 3: ICU 
admission from RSV hospitalization in infants
Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be 
interpreted in this context.Last name first 
author, 
Publication 
yearAge 
mean 
(SD), 
yearsN 
interventionN 
comparisonComparator 
VaccineAbsolute 
difference/effect 
estimate (95% CI)Study 
limitations 
(Risk of Bias)
Data received 
directly from 
the 
manufacturer29.0 
(5.7)3495 3480 Placebo 86 fewer per 
100,000 (176 
fewer to 251 
more)None
129Summary of Studies Reporting Outcome 4: Mechanical 
ventilation from RSV hospitalization in infants
Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be 
interpreted in this context.Last name first 
author, 
Publication 
yearAge 
mean 
(SD), 
yearsN 
interventio
nN 
comparisonComparato
r VaccineAbsolute 
difference/effect 
estimate (95% 
CI)Study 
limitations 
(Risk of Bias)
Data received 
directly from 
the 
manufacturer29.0 
(5.7)3495 3480 Placebo 144 fewer per 
100,000 (144 
fewer to 13 more)None
130Summary of Studies Reporting Outcome 5: RSV -associated 
death in infants 
Last name first 
author, 
Publication 
yearAge 
mean 
(SD), 
yearsN 
interventionN 
compariso
nComparator 
VaccineAbsolute 
difference/eff
ect estimateStudy 
limitations 
(Risk of Bias)
Kampmann B, 
et al.29.0
(5.7)3495 3480 Placebo Not estimable 
1 death in a 
placebo 
recipientNone
Phase 2b RCT, 
unpublished18-49 
(range)114 116 Placebo Not estimable 
0 deaths in trialNone
131Summary of Studies Reporting Outcome 6: All -cause 
medically attended lower respiratory tract infection in 
infants 
Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be 
interpreted in this context.Last name first 
author, 
Publication 
yearAge 
mean 
(SD), 
yearsN 
interventio
nN 
comparisonComparator 
VaccineAbsolute 
difference/effect 
estimate 
(99.17% CI)Study 
limitations 
(Risk of Bias)
Kampmann B, 
et al.29.0 
(5.7)3495 3480 Placebo 289 fewer per 
100,000 (2,241 
fewer to 2,068 
more)None
132Summary of Studies Reporting Outcome 7: All -cause 
hospitalization for lower respiratory tract infection in 
infants
Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be 
interpreted in this context.Last name first 
author, 
Publication 
yearAge 
mean 
(SD), 
yearsN 
interventio
nN 
comparisonComparator 
VaccineAbsolute 
difference/effect 
estimate (95% 
CI)Study 
limitations 
(Risk of Bias)
Data received 
directly from 
the 
manufacturer29.0 
(5.7)3495 3480 Placebo 631 fewer per 
100,000 (1,109 
fewer to 44 
more)None
133Summary of Studies Reporting Outcome 8: Serious adverse 
events in pregnant people 
Last name first 
author, 
Publication 
yearAge 
mean 
(SD), 
yearsN 
interventionN 
compariso
nComparato
r VaccineRelative 
difference/effect 
estimateStudy 
limitations 
(Risk of Bias)
Kampmann B, 
et al.29.0 
(5.7)3682 3675 Placebo RR: 1.07 (0.96, 
1.19)None
Phase 2b RCT 27.1
(5.2)115 117 Placebo RR: 0.51 (0.21, 
1.21)None
134Summary of Studies Reporting Outcome 9: Reactogenicity 
(grade 3+) in pregnant people 
Last name 
first author, 
Publication 
yearAge 
mean 
(SD), 
yearsN 
interventio
nN 
comparisonComparato
r VaccineRelative 
difference/effect 
estimateStudy 
limitations 
(Risk of Bias)
Kampmann B, 
et al.29.0 
(5.7)3663 3640 Placebo RR: 0.99 (0.74, 
1.34)None
Phase 2b RCT 27.1
(5.2)114 117 Placebo RR: 0.51 (0.10, 
2.75)None
135Summary of Studies Reporting Outcome 10: Serious 
adverse events in infants 
Last name first 
author, 
Publication yearAge median 
(range)N intervention N comparison Comparator 
VaccineRelative 
difference/effect 
estimateStudy 
limitations 
(Risk of Bias)
Kampmann B, 
et al. 11.97 
months 
(0.0, 24.3) 3568 3558 Placebo RR: 1.00 (0.90, 
1.11)None
Phase 2b RCT 114 116 Placebo RR: 1.10 (0.77, 
1.57)None
136Summary of Studies Reporting Outcome 11: Preterm birth
Last name first 
author, 
Publication yearAge mean 
(SD)N intervention N comparison Comparator 
VaccineRelative 
difference/effect 
estimateStudy 
limitations 
(Risk of Bias)
Kampmann B, 
et al.11.97 
months 
(0.0, 24.3)3568 3558 Placebo RR: 1.19 (0.97, 
1.45)None
Phase 2b RCT 115 117 Placebo RR: 2.03 (0.52, 
7.94)None
137Grade Summary of Findings Table -Benefits
№ of 
studiesStudy designRisk of 
biasInconsistency Indirectness ImprecisionOther 
considerationsIntervention ComparisonRelative
(CI)Absolute
(CI)Importance Certainty
Medically attended RSV -associated lower respiratory infection in infants
1 Randomized 
studiesNot 
seriousNot serious Not serious Not serious None 57/3495 (1.6%) 117/3480 
(3.4%)0.487 
(97.58% CI: 
0.332, 0.706)1,725 fewer per 
100,000 (988 to 
2,246 fewer)Critical High
23.1% 11,850 fewer per 
100,000 (6,791 to 
15,431 fewer)
11.0% 5,643 fewer per 
100,000 (3,234 to 
7,348 fewer)
Hospitalizations RSV -associated lower respiratory infection in infants
1 Randomized 
studiesNot 
seriousNot serious Not serious Serious None 19/3495 (0.5%) 44/3480 (1.3%) 0.432 
(99.17% CI: 
0.193, 
0.899)718 fewer per 
100,000 (128 to 
1,020 fewer)Critical Low
1.9% 1,051 fewer per 
100,000 (187 to 
1,493 fewer)
ICU admission from RSV hospitalization
1 Randomized 
studiesNot 
seriousNot serious Not serious Very serious None 4/3495 (0.1%) 7/3480 (0.2%) 0.571 (95% 
CI: 0.123, 
2.248)86 fewer per 
100,000 (176 fewer 
to 251 more)Important Low
0.7% 285 fewer per 
100,000 (583 fewer 
to 830 more)
138Grade Summary of Findings Table -Benefits
№ of 
studiesStudy 
designRisk of 
biasInconsistency Indirectness ImprecisionOther 
considerationsIntervention ComparisonRelative
(CI)Absolute
(95% CI)Importance Certainty
Mechanical ventilation from RSV hospitalization
1 Randomized 
studiesNot 
seriousNot serious Not serious Very serious None 0/3495 (0.0%) 5/3480 (0.1%) 0.001 
(95% CI: 
0.001, 
1.091)144 fewer 
per 100,000 
(144 fewer 
to 13 more)Important Low
0.2% 209 fewer 
per 100,000 
(209 fewer 
to 19 more)
All-cause medically attended lower respiratory tract infection in infants
1 Randomized 
studiesNot 
seriousNot serious Not serious Serious None 392/3495 
(11.2%)402/3480 
(11.6%)0.975 
(99.17% CI: 
0.806, 
1.179)289 fewer 
per 100,000 
(2,241 fewer 
to 2,068 
more)Important Moderate
All-cause hospitalization for lower respiratory tract infection in infants
1 Randomized 
studiesNot 
seriousNot serious Not serious Serious None 54/3495 (1.5%) 76/3480 (2.2%) 0.711 (95% 
CI: 0.492, 
1.010)631 fewer 
per 100,000 
(1,109 fewer 
to 44 more)Important Moderate
139Grade Summary of Findings Table -Harms
№ of 
studiesStudy designRisk of 
biasInconsistency Indirectness ImprecisionOther 
considerationsIntervention comparisonRelative
(95% CI)Absolute
(95% CI)Importance Certainty
Serious adverse events in pregnant women
2 Randomized 
studiesNot 
seriousNot serious Serious Serious None 605/3797 
(15.9%)572/3792 
(15.1%)1.06 
(0.95, 
1.17)905 more 
per 100,000 
(754 
fewer to 
2,564 more)Critical Low
Reactogenicity (3+ or higher) in pregnant women
2 Randomized 
studiesNot 
seriousNot serious Serious Not serious None 85/3777 
(2.3%)87/3757 (2.3%) 0.97 
(0.72, 
1.31)69 fewer per 
100,000 
(648 fewer 
to 718 more)Important Moderate
Serious adverse events in infants
2 Randomized 
studiesNot 
seriousNot serious Serious Serious None 666/3682 
(18.1%)661/3674 
(18.0%)1.01 
(0.91, 
1.11)180 more 
per 100,000 
(1,619 fewer 
to 1,979 
more)Critical Low
Preterm birth
2 Randomized 
studiesNot 
seriousNot serious Serious Very serious None 207/3683 
(5.6%)172/3675 
(4.7%)1.20 
(0.99, 
1.46)936 more 
per 100,000 
(47 fewer to 
2,153 more)Critical Very low