03 RSV Mat Ped Fleming Dutra 508

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Centers for Disease Control and Prevention
Evidence to Recommendations Framework: 
Pfizer Maternal RSVpreF Vaccine
Katherine 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
June 22, 2023
2Evidence to Recommendations (EtR) Framework
Policy Question
▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose 
IM given 24 –36 weeks gestation) be recommended for pregnant people 
to prevent RSV disease in infants?
RSVpreF is a bivalent recombinant stabilized prefusion F protein subunit vaccine
3Evidence to Recommendations (EtR) Framework
PICO Question
▪Population Pregnant people 24 –36 weeks gestation
Intervention Pfizer RSVPreF Vaccine
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
4Evidence to Recommendations (EtR) Framework
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 variability in how patients value the outcome?
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 in the impact of the intervention on health equity?
EtRDomain: Public Health Problem
Is the problem of public health importance?
6RSV is the leading cause of hospitalization in U.S. 
infants1
▪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 conditions3
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
7Seasonality of RSV transmission —National Respiratory 
and Enteric Virus Surveillance System, NREVSS1, 2017 –
2020
0510152025
27293133353739414345474951 135791113151719212325
Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun% PCR results RSV -positive
Epidemiologic week
Abbreviation : PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm
* 3-week centered moving averages of percentage of RSV -positive PCR results nationwide. The black dotted line represents the thr eshold for a seasonal epidemic (3% RSV -positive laboratory PCR results). 
8Changes in seasonality of RSV transmission following 
SARS -CoV2 introduction —NREVSS1, 2017 –2023
0510152025
27293133353739414345474951 135791113151719212325
Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun% PCR results RSV -positive
Epidemiologic week2017 –18 2018 –19 2019 –20 2020 –21 2021 –22 2022 –23
Abbreviation : PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm
* 3-week centered moving averages of percentage of RSV -positive PCR results nationwide. The black dotted line represents the thr eshold for a seasonal epidemic (3% RSV -positive laboratory PCR results). 
9Public Health Problem -Work Group Interpretation
▪Is RSV among infants of public health importance? 
NoProbably 
NoProbably 
YesYes VariesDon’t 
know
EtRDomain: 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?
11GRADE Outcomes, Importance, and Data Sources: 
Pfizer maternal RSVpreF vaccine
Outcome 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 No data
Mechanical ventilation from RSV hospitalization in infants Important No data
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 No data
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) Critical Phase 3 and phase 2b2RCT
RCT = Randomized -controlled trial
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 were included
12Efficacy estimates and concerns in certainty of 
assessment, benefits : Pfizer maternal RSVpreF vaccine
Outcome Importance1 Data sources Manufacturer 
calculated vaccine 
efficacy (97.58% or 
99.17% CI)2Concerns in certainty 
assessment
Benefits
Medically attended RSV -associated lower respiratory tract infection in 
infants (0 –180 days)Critical Phase 3 RCT 51.3% (29.4, 66.8) None
Hospitalization for RSV -associated lower respiratory tract infection in 
infants (0 –180 days)Critical Phase 3 RCT 56.8% (10.1, 80.7) Imprecision (serious)3
ICU admission from RSV hospitalization in infants Important No data
Mechanical ventilation from RSV hospitalization in infants Important No data
RSV-associated death in infants Important Phase 3 and phase 2b4
RCT1 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% ( -17.9, 19.4) Imprecision (serious)3
All-cause hospitalization for lower respiratory tract infection in infants Important No data
RCT = Randomized -controlled trial
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. 97.58% confidence interval used for medically attended RSV -associated lower 
respiratory tract infection in infants, 99.17% confidence interval used for other endpoints. 
3 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered
4  Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial were included
13Efficacy estimates and concerns in certainty of 
assessment, harms : Pfizer maternal RSVpreF vaccine
Outcome Importance1Data sources Relative Risk2 (95% 
confidence interval)Concerns in certainty 
assessment
Harms
Serious adverse events in pregnant people Critical Phase 3 and 
phase 2b2RCT1.06 (0.95, 1.17) Imprecision (serious)3
Reactogenicity (grade 3+) in pregnant people Important Phase 3 and 
phase 2b2RCT0.97 (0.72, 1.31) Indirectness (serious)4
Serious adverse events in infants Critical Phase 3 and 
phase 2b2RCT1.01 (0.91, 1.11) Imprecision (serious)3
Preterm birth (<37 weeks) Critical Phase 3 and 
phase 2b2RCT1.20 (0.99, 1.46) Imprecision (very serious)5
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
3 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered
4 Serious concern for indirectness as these data only includes systemic reactions 
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 not 
meeting optimal information size requirements
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 No data Not evaluated
Mechanical ventilation from RSV hospitalization in 
infants Important No data Not evaluated
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 No data Not evaluated
Harms
Serious adverse events in pregnant people Critical RCT (2) SAEs in pregnant people were balanced between vaccine and placebo 
groupsModerate
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 Moderate
Preterm birth (<37 weeks) Critical RCT (2) Preterm births were unbalanced between vaccine and placebo groups Low
15Summary of GRADE: Pfizer maternal RSVpreF vaccine
15Overall 
evidence type: 
Low

16Outcome: Preterm births (n=2 studies), Pfizer maternal 
RSVpreF vaccine
16Publication 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)
*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
17Outcome: Preterm births (n=2 studies), Pfizer maternal 
RSVpreF vaccine
▪Measures of effect
–Relative risk: 1.20 (0.99, 1.46)
–Absolute risk*:  9 more per 1,000 (from 0 fewer to 22 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
▪Evidence type: Low
*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.
18Preterm birth rates in maternal RSV vaccine clinical 
trials: GSK
▪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
▪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 unclear
Study vaccine given at 240/7to 340/7weeks 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 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)
19Preterm birth rates in maternal RSV vaccine clinical 
trials: Novavax
▪Phase 3 clinical trial in 4,636 women randomized 2:1, vaccine to placebo
▪Vaccine formulation: 120μg of recombinant RSV F protein nanoparticle vaccine 
adsorbed to 0.4mg of aluminum (Novavax vaccine was not stabilized in the 
prefusion form)
▪Maternal vaccine did not reach primary efficacy endpoints and thus did not move 
forward, but there were no safety concerns (preterm births or other) in this trial 
Preterm Birth Definition Preterm Birth in Vaccine group, 
n (%)
N=2,986Preterm Birth in Placebo, 
n (%)
N=1,554
<37 weeks among infants* 175 (5.9%) 96 (6.2%)
*Study vaccine given at ≥28 through 36 weeks and 0 days gestation. Data from Table 1 among infants for whom the protocol -mandated dating ultrasonography result was 
available for calculating gestational age.
1. Madhi SA, Polack FP , Piedra PA, et al. Respiratory syncytial virus vaccination during pregnancy and effects in infants. N Engl J Med 2020;383:426 -39. DOI: 
10.1056/NEJMoa1908380
20Preterm birth and low birth weight outcomes in 
maternal RSV vaccine clinical trials: Pfizer RSVpreF 
vaccine phase 3 trial data
*Confidence intervals not reported for these estimates. 
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)RSVpreF vaccine group
N=3,568Placebo group
N=3,558
Preterm birth (<37 weeks) 5.7% (95% CI: 4.9%, 6.5%) 4.7% (95% CI: 4.1%, 5.5%)
Late preterm birth (≥34 to 
<37 weeks)5.0%* 4.4%*
Low birth weight ( ≤2500g) 5.1% (95% CI: 4.4%, 5.8%) 4.4% (95% CI: 3.7%, 5.0%) 
21Infant deaths in maternal RSV vaccine clinical trials: 
Pfizer RSVpreF vaccine phase 3 trial data
▪Infant deaths (all -cause) through 24 months of age: 5 (0.1%) in the 
RSVpreF group vs 12 (0.3%) in placebo group
▪Among infant deaths in the RSVpreF group
–4 of 5 deaths were considered unrelated to the investigational product 
by FDA
–1 death was in an infant with extreme prematurity (27 weeks) and 
prematurity -related complications, and FDA was unable to exclude 
possibility of relationship to investigational product
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)
22
Time from Vaccination to Birth Among Preterm and 
Term Births, Infant Participants, Safety Population: 
Pfizer RSVpreF vaccine phase 3 trial data
▪Median gestational age at vaccination in trial was 31 weeks
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)
23Subgroup analysis of gestational age at birth among 
live births by country income level : Pfizer RSVpreF
vaccine phase 3 trial data
▪In high -income countries, preterm birth rate was 5.1% (126/2494) in 
RSVpreF recipients vs 5.1% (126/2484) placebo recipients
▪Imbalance was most prominent in upper middle income countries: 7.5% 
(72/964) in RSVpreF recipients vs. 4.1% (39/961) in placebo recipients
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
24
Subgroup analysis of gestational age at birth among 
live births, South Africa and US: Pfizer RSVpreF vaccine 
phase 3 trial data
Trial was conducted in 18 countries. 
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA▪In South Africa, preterm birth rate was 8.3% (39/469) in RSVpreF recipients 
vs 4.0% (19/471) placebo recipients
▪In US, preterm birth rate was 5.7% (94/1654) in RSVpreF recipients vs. 5.3%
(87/1644) in placebo recipients
25VRBPAC discussion regarding preterm births: Pfizer 
RSVpreF vaccine 
▪An imbalance was seen in preterm births in both phase 2b and phase 3 
trials, but the imbalance was not statistically significant
▪Preterm birth rate in trials was lower than background incidence rate of 
preterm birth (~10% in US), but the trial had multiple exclusion criteria 
selecting for a population at lower risk of preterm birth
▪Trial was underpowered to detect a 20% relative increase in preterm birth
181st Meeting of the Vaccines and Related Biological Products Advisory Committee –YouTube
Preterm Birth | Maternal and Infant Health | Reproductive Health | CDC
26VRBPAC discussion regarding preterm births: Pfizer 
RSVpreF vaccine (cont.)
▪Imbalance was still present but less pronounced when comparing 
prevalence of low birth weight
▪Most preterm births were late preterm ( ≥34 to <37 weeks)
▪Most preterm births were >30 days after vaccination
▪Preterm birth imbalance was most prominent in a single country, South 
Africa
▪VRBPAC voted 14 -0 that the data supported effectiveness of Pfizer 
maternal RSVpreF and voted 10 -4 that data supported safety
181st Meeting of the Vaccines and Related Biological Products Advisory Committee -YouTube
27Other considerations: Inflammatory neurologic events 
Pfizer RSVPreF Vaccine
▪Same Pfizer RSV vaccine, formulation and dose approved for use in older adults
▪Within the main phase 3 trial for this product among adults ages ≥ 60 years (RENOIR) 
a potential neurologic safety signal was identified
▪A total of 3 cases of potential inflammatory neurologic events were recorded among 
20,255 investigational vaccine recipients across all clinical trials. No cases were 
observed among placebo recipients.
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/06 -RSV-Adults -Melgar -508.pdf)
28Other considerations: Inflammatory neurologic events 
Pfizer RSVPreF Vaccine (cont.)
▪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)2
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 
29Benefits and Harms Pfizer Maternal RSVPreF Vaccine
▪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 
Minimal Small Moderate Large Varies Don’t know
30Benefits and Harms Pfizer Maternal RSVPreF Vaccine
▪How substantial are the undesirable anticipated effects?
–How substantial are the anticipated effects for:
•Serious adverse events in pregnant women 
•Reactogenicity (3+ or higher) in pregnant women 
•Serious adverse events in infants 
•Preterm birth 
Minimal Small Moderate Large Varies Don’t know
Minority Opinion
31Benefits and Harms Pfizer Maternal RSVPreF Vaccine
▪Do the desirable effects outweigh the undesirable effects?
–What is the balance between the desirable effects relative to the 
undesirable effects?
Favors intervention (Pfizer Maternal RSVPreF 
Vaccine)
Favors comparison (No intervention)
Favors both
Favors neither
Unclear
EtRDomain: 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?
33University of Iowa, RAND, and CDC Values Survey, 
December 21, 2022 -January 2, 2023
▪523 participants
–Pregnancy status:*
•58.1% currently pregnant
•44.9% given birth in the last 12 months
–Race and Ethnicity:*
•66.0% Non -Hispanic White 
•16.5% Non -Hispanic Black
•9.8% Hispanic
•7.7% Other Race/Ethnicity
▪68% of respondents had knowledge of RSV prior to taking survey
*Participants were able to select all applicable answer choices.
CDC and University of Iowa/RAND survey, unpublished
3461% of respondents said they ‘definitely’ or ‘probably’ 
would get an RSV vaccine while pregnant
CDC and University of Iowa/RAND survey, unpublished
35Among 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
CDC and University of Iowa/RAND survey, unpublished
3622% of respondents did not want any vaccines or were unsure about how 
many vaccines they would be willing to get in the same healthcare visit 
during pregnancy
Prefer not to say
0%Unsure  
10%No vaccines
12%One vaccine
17%Two vaccines
32%
Three vaccines
9%Four vaccines
20%
0%10%20%30%40%50%60%70%80%90%100%% of respondents (n=523)
CDC and University of Iowa/RAND survey, unpublished
37
Tdap vaccine coverage among pregnant women (n=838), 
by race and ethnicity —Internet Panel Survey, United 
States, April 2020 –April 2022 
Flu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC
38Values
▪Criterion 1: Do pregnant people feel that the desirable effects are large 
relative to undesirable effects?
No Probably No Probably Yes Yes Varies Don’t know
39Values
▪Criterion 2: Is there important uncertainty about, or variability in, how 
much pregnant people value the main outcomes?
Important uncertainty or variability
Probably important uncertainty or variability
Probably not important uncertainty or variability
No important uncertainty or variability
No known undesirable outcomes
Minority Opinion
EtRDomain: Acceptability
Is the intervention acceptable to key stakeholders?
41Maternity healthcare professionals survey —England, 
2019
▪Obstetrician and midwife support of RSV vaccine, if it was routinely 
recommended:
–47% definitely
–34% likely
–14% not sure
–4% unlikely
–0.5% very unlikely
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 38(9):p 944 -951, September 2019. | DOI: 
10.1097/INF.0000000000002384
42Acceptability
▪Is RSV prevention with Pfizer maternal RSVPreF vaccine acceptable to 
key stakeholders?
No Probably No Probably Yes Yes Varies Don’t know
EtRDomain: Feasibility
Is the intervention feasible to implement?
44Storage 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
ShowLabeling.aspx (pfizer.com) and Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Bivalent RSV Prefusion F 
Vaccine for Maternal Immunization to Protect Infants (fda.gov)
45Timing of RSVPreF vaccination during pregnancy
▪Trial dosing was between 24 through 36 weeks gestation
▪Median gestational age at vaccination in phase 3 trial was 31 weeks1
▪Administration of maternal RSVPreF vaccine during regularly scheduled 
prenatal visits and bundling with recommended screening tests and 
other recommended vaccinations could also improve feasibility
–Tdap recommended every pregnancy, preferably during the early part 
of gestational weeks 27 through 362
–Glucose challenge test recommended at 26 -28 weeks gestation3
1. FDA. Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safet y of Respiratory Syncytial 
Virus Vaccine (ABRYSVO) (fda.gov)
2. CDC, https://www.cdc.gov/vaccines/vpd/dtap -tdap -td/hcp/recommendations.html
3. US HHS OASH, https://www.womenshealth.gov/pregnancy/youre -pregnant -now -what/prenatal -care -and-
tests#:~:text=Typically%2C%20routine%20checkups%20occur%3A,for%20weeks%2036%20to%20birth
46Efficacy against medically attended RSV -associated 
lower respiratory tract disease by gestational age at 
vaccination 
Subgroup Gestational Age at 
VaccinationRSVpreF 
(N= 3495) 
nRSVpreF 
(N= 3495) 
# cases (%)Placebo 
(N=3480)
nPlacebo 
(N=3480) 
# cases (%)VE (%) (95% CI)
Interim analysis at 180 days -- -- -- -- --
≥24 weeks to <28 weeks 890 22 (2.5) 866 27 (3.1) 20.7 ( -44.6, 57.0)
≥28 weeks to <32 weeks 1030 11 (1.1) 1070 35 (3.3) 67.4 (34.2, 85.0)
≥32 weeks to ≤36 weeks 1572 24 (1.5) 1539 55 (3.6) 57.3 (29.8, 74.7)
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)Source: adapted from Pfizer 1008 CSR
Abbreviations: RSV= respiratory syncytial virus; VE= vaccine efficacy; CI= confidence interval
Note: this subgroup analysis did not appear in the FDA Briefing Document 
47Potential considerations for timing of RSV vaccine 
dosing during the year
▪RSV vaccine dosing could be implemented for pregnant people as a 
seasonal campaign or year -round 
▪Year -round dosing
–Simplify implementation and potentially increase vaccine uptake
–Protect infants in the event of atypical RSV seasonality
–Is less cost -effective
▪Limited benefit for doses given during March -May changes benefit/risk 
calculation
48Potential considerations for timing of RSV vaccine 
dosing during the year (cont.)
▪Some U.S. jurisdictions have different or less predictable RSV 
seasonality, and recommendations for RSV vaccine dosing in those 
jurisdictions would need to account for that
–Tropical climates: parts of Florida, Puerto Rico, U.S. Virgin Islands, 
Hawaii, Guam, and U.S. -affiliated Pacific Islands
–Alaska: RSV seasonality is less predictable, and the duration of RSV 
activity is often longer than the national average
49Simultaneous administration of RSV vaccines in 
pregnant people
▪Pregnant people may potentially be eligible to receive RSV, Tdap, 
COVID -19, and influenza vaccines at same visit
▪No available data on simultaneous administration of RSVpreF vaccine in 
pregnant people and limited data in non -pregnant people
▪According to CDC’s immunization general best practices, age -
appropriate vaccinations can be administered simultaneously, with two 
specific exceptions1,2
1. In persons with anatomic or functional asplenia and/or HIV infection, quadrivalent meningococcal conjugate vaccine (MCV4) -D (MenACWY -D, Menactra ) and 
pneumococcal conjugate vaccine (PCV)13 (PCV13, Prevnar 13) should not be administered simultaneously. In patients recommended toreceive both PCV13 and PPSV23, 
the 2 vaccines should not be administered simultaneously. ACIP Timing and Spacing Guidelines for Immunization | CDC
50Available data on simultaneous administration with 
Pfizer RSVpreF vaccine
▪Pfizer Phase 2b study in healthy non-pregnant women ages 18 -49 on 
coadministration of Tdap and Pfizer RSVpreF1
–Coadministration of Tdap and Pfizer RSVpreF led to decreased immune response to 
pertussis components (i.e. non -inferiority criteria were not met)
▪Phase 3 study in non-pregnant adults ages ≥65 years on coadministration of 
RSVpreF and adjuvanted seasonal quadrivalent influenza vaccine2
–Non-inferiority criteria were met for antibody titers against all 4 influenza strains, 
as well as RSV -A and RSV -B
▪No safety concerns in either trial
▪Neither trial evaluated efficacy (not powered)
1. Peterson et. al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When Coadministered With a Te tanus, Diphtheria, and Acellular Pertussis 
Vaccine, The Journal of Infectious Diseases, Volume 225, Issue 12, 15 June 2022, Pages 2077 –2086 ,https://doi.org/10.1093/infdis/jiab505
2. Safety and Immunogenicity of RSVpreF Coadministered With SIIV in Adults ≥65 Years of Age -Full Text View -ClinicalTrials.gov
51Pertussis immunogenicity and co -administration in 
adolescents and adults
▪There is no accepted correlate of protection for pertussis vaccination
–In the absence of a correlate of protection, non -inferiority is used to assess 
immunogenicity of co -administration
–Clinical significance of failing to meet non -inferiority for pertussis is unclear 
▪Some studies in adolescents and adults looking at Tdap coadministration 
with other vaccines, including meningococcal and influenza vaccines, failed 
to demonstrate non -inferiority against at least one pertussis antibody, but 
coadministration is still recommended
▪Unclear how this might impact protection against pertussis from maternal 
Tdap when co -administered with RSVpreF
Liang JL, Tiwari T, Moro P , et al. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recom men dations of the Advisory Committee on 
Immunization Practices (ACIP). MMWR Recomm Rep 2018;67(No. RR -2):1–44. DOI: http://dx.doi.org/10.15585/mmwr.rr6702a1 external icon
52
Place of Flu, Tdap, COVID -19 Vaccination among 
Pregnant Women, United States, Internet Panel 
Survey, April 2022
Flu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC“Other place” includes other medical or non -medical place, including school or special site for COVID -19 vaccination
53Availability of vaccines to pregnant people by practice 
type
▪Survey of health care providers conducted in Fall 2022
Provider type (%)
Total 
(n=1,538)Family 
Practitioner/ 
Internist Pediatrician OB/GYN NP/PA
Tdap 72% 73% 79% 74% 58%
COVID -19 53% 56% 66% 40% 49%
Influenza 81% 85% 83% 74% 67%
Ob/Gyn =Obstetrician -Gynecologist; NP/PA: Nurse Practitioner or Physician’s Assistant 
Unpublished data, Fall 2022 DocStylesProportion of practices that offer or administer vaccinations on site to pregnant patients
54Feasibility
▪Is Pfizer Maternal RSVPreF vaccine feasible to implement among 
pregnant people at 24-36 weeks gestation?
No Probably No Probably Yes Yes Varies Don’t know
Minority Opinion
EtRDomain: Resource Use
Is the intervention a reasonable and efficient allocation of resources?
56Summary of Economic Analysis of RSVPreF in Pediatric 
Populations
▪RSVPreF has the potential to be cost -effective
–Base case ICER: $214,087/QALY 
▪Results sensitive to:
–Rate of prematurity 
–Cost per dose
–Efficacy
–QALYs lost
–Timing of vaccination: year -round vs seasonal (e.g., June -February)
ICER: Incremental cost -effectiveness ratio; QALY: Quality -adjusted life year
57Resource Use
▪Is Pfizer Maternal RSVPreF vaccine use among pregnant people at 24 –
36 weeks gestation a reasonable and efficient allocation of resources?
No Probably No Probably Yes Yes Varies Don’t know
EtRDomain: Equity
What would be in the impact of the intervention on health equity?
59Population -based hospitalization rates among infants <6 months 
old with laboratory -confirmed RSV by race and ethnicity, RSV -NET, 
2018 –2019 to 2021 –2022
▪Hospitalization rates among infants <6 months old differ by race and ethnicity but vary by 
season 
▪Rates were not adjusted for RSV testing practices and thus may underrepresent RSV 
hospitalization rates but should not affect distributions by race and ethnicity 
RSV-NET: unpublished data. Surveillance was conducted from October –April for the 2018 –19 and 2019 –20 seasons, October –September for the 2020 –21 season, and October –
September excluding May –June for the 2021 –22 season. Rates were not adjusted for RSV testing practices; testing practices may di ffer by racial and ethnic groups and may have 
changed over time. Black, White, Asian/Pacific Islander children were categorized as non -Hispanic; Hispanic children could be of any race. 
0246810121416
2018–2019 2019–2020 2020–2021 2021–2022Rate per 1,000 population
Non-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian/Pacific Islander
6001234567
2018–2019 2019–2020 2020–2021 2021–2022Rate per 1,000 population
Non-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian/Pacific IslanderPopulation -based ICU admission rates among infants <6 months 
old with laboratory -confirmed RSV by race and ethnicity, RSV -
NET, 2018 –2019 to 2021 –2022
RSV-NET: unpublished data. Surveillance was conducted from October –April for the 2018 –19 and 2019 –20 seasons, October –September for the 2020 –21 season, and October –
September excluding May –June for the 2021 –22 season. Rates were not adjusted for RSV testing practices; testing practices may di ffer by racial and ethnic groups and may have 
changed over time. Black, White, and Asian/Pacific Islander children were categorized as non -Hispanic; Hispanic children could b e of any race.ICU admission rates among Non -Hispanic Black infants <6 months 
old were 1.2–1.6x higher than among Non -Hispanic White infants

61Seasonal rate of RSV -associated hospitalizations per 
1,000 children among American Indian and Alaska 
Native children <5 years of age, Nov 2019 -May 2020 
(SuNA )*
*Hartman et al, RSV2022 12thInternational Symposium, Belfast 9/29/2022 -10/2/2022; Atwell et al. RSV among American Indian and Alaska Native children: 2019 -20 
(manuscript in press) SuNA = RSV Surveillance among Native American Persons
**Incidence of RSV -associated hospitalization in 2019 -2020 included for comparison. NVSN = New Vaccine Surveillance Network.
Age  Chinle, Arizona   Whiteriver, 
Arizona  Anchorage, Alaska  Yukon -Kuskokwim 
Delta, Alaska  NVSN** for 
comparison  
0-5 Months  83.0 (52.0, 132.5)  70.4 (36.3, 136.6)  35.7 (20.4, 62.6)  132.3 (98.2, 178.1)  21.6 (20.0 , 23.3)  
6-11 Months  61.6 (35.9, 105.8)  90.1 (50.0, 162.3)  0.0 (0.0, 10.8)  91.6 (64.0, 131.0)  8.2 (7.1 , 9.3) 
0-11 Months  71.8 (50.4, 102.4)  80.6 (51.9, 125.2)  19.2 (11.2, 33.0)  112.2 (89.3, 141.0)  14.9 (13.9 , 16.0)  
12-23 Months  42.1 (27.2, 65.3)  38.7 (22.0, 68.1)  15.6 (8.7, 27.7)  26.4 (16.6, 41.8)  4.5 (3.9 , 5.2) 
24-59 Months  10.9 (6.8, 17.4)  8.2 (4.2, 16.0)  1.1 (0.3, 3.8)  5.9 (3.2, 10.9)  1.2 (1.2 , 1.5) 
0-59 Months  27.2 (21.4, 34.4)  25.4 (18.7, 34.5)  7.7 (5.3, 11.1)  32.7 (26.9, 39.7)  4.6 (4.3, 4.8) 
 
62Insurance coverage for vaccinations among pregnant 
people
▪All ACIP -recommended vaccinations are covered without cost -sharing for adults in 
the Affordable Care Act (ACA) adult group who receive all essential health benefits1
▪Beginning on October 1, 2023, coverage of all approved ACIP -recommended adult 
vaccines and vaccine administration, without cost sharing, will be mandatory for 
both Medicaid and the Children’s Health Insurance Program under section 11405 of 
the Inflation Reduction Act (IRA) (Pub. L. 117 -169). 
▪Currently, most state Medicaid agencies cover at least some ACIP -recommended 
adult immunizations for those not subject to essential health benefits, but may not 
cover all recommended vaccines.
1 Quality of Care Vaccines | Medicaid
63Medicaid coverage among pregnant people
▪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 2020, 42.0% of mothers had Medicaid at the time of birth2
▪In 2020, about 1 in 9 (11.6%) women of childbearing age (aged 15 -44 
years) was uninsured in the United States3
1 Medicaid Coverage for Women | KFF
2 Medicaid coverage of births: United States, 2020 | PeriStats | March of Dimes
3 Uninsured women: United States, 2010 -2020 | PeriStats | March of Dimes
64Equity
▪What would be the impact of Pfizer Maternal RSVPreF vaccine on 
health equity?
Reduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t know
Summary
66Evidence 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? Moderate to large
How substantial are the undesirable anticipated effects? Small vs Don’t Know
Do the desirable effects outweigh the undesirable effects? Favors intervention vs Unclear
Values Does the target population feel the desirable effects are large 
relative to the undesirable effects?Probably Yes
Is there important variability in how patients value the 
outcome?Probably important 
uncertainty or variability 
Acceptability Is the intervention acceptable to key stakeholders? Probably yes or Yes
Feasibility Is the intervention feasible to implement? Probably yes 
Resource Use Is the intervention a reasonable and efficient allocation of 
resources?Probably yes 
Equity What would be in the impact of the intervention on health 
equity?Probably increased 
67Evidence 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
68Evidence 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
69Summary of WG interpretations 
▪Efficacious vaccine that can prevent RSV lower respiratory tract infection in 
young infants
▪WG expressed concern that the Pfizer trial was underpowered to detect a 
20% difference in preterm births between vaccine and placebo recipients
▪Interpretation of these overarching themes varied:
–Some members of the WG expressed concern that the data were insufficient to 
determine the safety of this vaccine 
–Others stressed this vaccine can provide benefit by preventing RSV lower 
respiratory tract infection in infants and the difference in preterm births was 
not statistically significant
70Summary of WG interpretations (cont.) 
▪Imbalance in preterm birth was most prominent in a single country, South 
Africa
▪Imbalance in preterm births was not seen in high -income countries
▪Imbalance was still present but less pronounced when comparing 
prevalence of low birth weight
▪Most preterm births were >30 days after vaccination
71Summary of WG interpretations (cont.) 
▪WG discussed considering a narrower recommended dosing window
–Some expressed support for starting dosing at a later gestational age within 
24–36-week window used in the trial as this could mitigate potential risk of 
early preterm birth until additional safety data are available
–Others expressed concern that this could leave preterm infants who are at 
higher risk of severe RSV disease unprotected
▪Aligning RSVpreF vaccine dosing during pregnancy with Tdap 
administration could improve feasibility
▪All WG members endorsed the importance of post -introduction vaccine 
safety monitoring
72ACIP Policy Question
▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose 
IM given 24 –36 weeks gestation) be recommended for pregnant people 
to prevent RSV disease in infants?
Summary of proposed clinical 
considerations for use of Pfizer RSVpreF
vaccine during pregnancy
74Proposed clinical considerations: Timing of dosing 
during pregnancy and simultaneous administration
▪Proposed dosing interval for RSVpreF vaccine is 24 –36 weeks (aligned with 
trials)
▪Healthcare providers could consider aligning RSVpreF vaccine dosing during 
pregnancy with Tdap administration for feasibility of implementation 
▪RSVpreF vaccine can be administered with other recommended vaccines 
(e.g., influenza, COVID -19) without regards to timing, including 
simultaneous vaccination on same clinic day
75Proposed clinical considerations: Timing of dosing 
during the year
▪RSVpreF vaccine should be offered to pregnant people during June -
February in the continental United States 
▪Healthcare providers can consider offering RSVpreF vaccine year -round 
–For ease of implementation
–If RSV seasonality is unpredictable
–In jurisdictions with different RSV seasonality than continental U.S.
76Proposed clinical considerations: Additional vaccine 
doses in subsequent pregnancies
▪Currently there are no data available on
–Efficacy of the first lifetime dose during subsequent pregnancies
–Safety of additional doses given in subsequent pregnancies
▪WG felt that it was too early 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 future
77Acknowledgements 
Jefferson 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 -Outcalt
Patricia Wodi
Sascha Ellington
78Note
Weacknowledge 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.
For more information, contact CDC
1-800-CDC-INFO (232 -4636)
TTY:  1 -888-232-6348    www.cdc.gov
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.

Extra slides for GRADE
Centers for Disease Control and Prevention
Grading of Recommendations, Assessment, 
Development, and Evaluation (GRADE): 
Pfizer Maternal RSVPreF Vaccine 
Update: May 19, 2023
82Evidence Retrieval, conducted as of April 10, 2023
Records 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)
*Medline (OVID), Embase (OVID), Cochrane Library, CINAHL ( EbscoHost ), Scopus, clinicaltrials.gov
83▪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.
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.GRADE Evidence Type
84GRADE Evidence Type
▪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.
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.
Benefits
86Outcome 1: Medically attended RSV -associated lower 
respiratory tract infection in infants (n=1 study)
▪ 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 ingredients
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.
87Outcome 1: Medically attended RSV -associated lower 
respiratory tract infection in infants (n=1 study)
▪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
▪Positive validated RT -PCR in central laboratory
▪Confirmed by endpoint adjudication committee (EAC)
SpO2= Peripheral capillary oxygen saturation 
88Outcome 1: Medically attended RSV -associated lower 
respiratory tract infection in infants (n=1 study)
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)
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 Bonferron i procedure), 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).
2This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <20%) 
89Outcome 1: Severe Medically attended RSV -associated 
lower respiratory tract infection in infants (n=1 study)
▪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
▪Positive validated RT -PCR in central laboratory
▪Confirmed by endpoint adjudication committee (EAC)
SpO2= Peripheral capillary oxygen saturation 
90Outcome 1: Severe Medically attended RSV -associated 
lower respiratory tract infection in infants (n=1 study)
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)
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 Bonferron i procedure), 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).
91GRADE: Medically attended RSV -associated lower 
respiratory infection in infants (n=1 study)
▪Measures of effect
–Relative Risk: 0.487 (0.332, 0.706)
–Absolute Risk1: 17 fewer per 1,000 (10 to 22 fewer); NNV: 59 (45, 100)
–Absolute Risk2: 119 fewer per 1,000 (68 to 154 fewer); NNV: 8 (6, 15)
–Absolute Risk3: 56 fewer per 1,000 (32 to 73 fewer); NNV: 18 (14, 31)
▪Concerns in certainty assessment: None
▪Evidence type: High
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 LRTI. 
3Calculated assuming 47.5% of ARI from Lively et al paper were LRTI ( Rainisch 2020 Vaccine )
NNV= Number needed to vaccinate
92Outcome 2: Hospitalization for RSV -associated lower 
respiratory tract infection in infants (n=1 study)
▪Phase 3 RCT, MATISSE1
▪A respiratory tract infection due to RSV that results in hospitalization
▪Confirmed by endpoint adjudication committee (EAC)
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.
93Outcome 2: Hospitalization for RSV -associated lower 
respiratory tract infection in infants (n=1 study)
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 
birth15/3495 37/3480 59.6% (26.6, 77.8) 59.5% (8.3, 83.7)
0–150 days after 
birth17/3495 39/3480 56.6% (23.4, 75.4) 56.4% (5.2, 81.5)
0–180 days after 
birth19/3495 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)
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 criter ionfor vaccine 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%) 
94GRADE: Hospitalization for RSV -associated lower 
respiratory tract infection in infants (n=1 study)
▪Measures of effect
–Relative risk: 0.432 (0.193, 0.899)
–Absolute risk1: 7 fewer per 1,000 (1 to 10 fewer); NNV: 143 (100, 1,000)
–Absolute risk2: 11 fewer per 1,000 (2 to 15 fewer); NNV: 91 (67, 500) 
▪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: Moderate
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)  
95Outcome 5: RSV -associated death in infants (n=2 
studies)
▪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 GRADE
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
96Outcome 6: All -cause medically attended lower 
respiratory tract infection in infants (n=1 study)
▪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 indrawing
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.SpO2= Peripheral capillary oxygen saturation 
97Outcome 6: All -cause medically attended lower 
respiratory tract infection in infants (n=1 study)
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)
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 criter ionfor vaccine efficacy was a
lower bound of the confidence interval >0%.
2This outcome did not meet success criterion (lower bound of CI was <0%) 
98GRADE: All-cause medically attended lower respiratory 
tract infection in infants (n=1 study)
▪Measures of effect
–Relative risk: 0.975 (0.806, 1.179)
–Absolute risk*: 3 fewer per 1,000 (22 fewer to 21 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: Moderate
*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.
Harms
100Outcome 8: Serious adverse events in pregnant people 
(n=2 studies)
▪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)
101Outcome 8: Serious adverse events in pregnant people 
(n=2 studies)
101Trial 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 t he 
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 re lated 
to the study intervention.
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
102GRADE: Serious adverse events in pregnant people 
(n=2 studies)
▪Measures of effect
–Relative risk: 1.06 (0.95, 1.17)
–Absolute risk*: 9 more per 1,000 (8 fewer to 26 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: Moderate
*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.
103Outcome 9: Reactogenicity (grade 3+) in pregnant 
people (n=2 studies)
▪Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly 
from manufacturer)
▪Participants reported local and systemic reactions up to 7 days after 
vaccination
104Outcome 9: Reactogenicity (grade 3+) in pregnant 
people 
104Trial Outcome Events/Vaccine
(n/N)Events/Placebo
(n/N)Relative Risk (95% CI)
Phase 3 Local events (grade 3+) 11/3660 (0.3%) 0/3639 (0%) 22.87 (1.35, 387.94)
Systemic events (grade 3+) 83/3663 (2.3%) 83/3640 (2.3%) 0.94 (0.70, 1.28)
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. 

105Outcome 9: Reactogenicity (grade 3+) in pregnant 
people (n=2 studies)
▪Measures of effect
–Relative risk: 0.97 (0.72, 1.31)
–Absolute risk*:  1 fewer per 1,000 (6 fewer to 7 more)
▪Concerns in certainty assessment: 
–Serious concern for indirectness as this data only includes systemic 
reactions 
▪Evidence type: Moderate
*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.
106Outcome 10: Serious adverse events in infants (n=2 
studies)
▪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 arm
107
Outcome 10: Serious adverse events in infants (n=2 
studies)
Trial 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 rec eipt 
of the investigational product. No non -fatal SAEs in infant participants were considered related to maternal vaccination by FDA.
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
108GRADE: Serious adverse events in infants (n=2 studies)
▪Measures of effect
–Relative risk: 1.01 (0.91, 1.11)
–Absolute risk*:  2 more per 1,000 (16 fewer to 19 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: Moderate
*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.
109Outcome 11: Preterm births (n=2 studies)
▪Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly 
from manufacturer)
–Gestational age at birth <37 weeks and <34 weeks
110Outcome: Preterm births (n=2 studies), Pfizer maternal 
RSVpreF vaccine
110Publication 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)
*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
111Outcome: Preterm births (n=2 studies), Pfizer maternal 
RSVpreF vaccine
▪Measures of effect
–Relative risk: 1.20 (0.99, 1.46)
–Absolute risk*:  9 more per 1,000 (from 0 fewer to 22 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
▪Evidence type: Low
*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.
GRADE additional slides
113Inclusion/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 obste tric 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 (eg, anaphylaxis) to any compone nt 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 (eg, 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 nancy 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 despositive 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 anned 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. Note: Licensed COVID -19 vaccines or COVID -19 vaccines 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.
114Inclusion/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.
115Inclusion/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 ar teritis 
(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.
116Inclusion/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.
117
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.
118Table 1. Demographics of phase 3 trial
118
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.
119Severity scale for local reactions and systemic events 
(maternal participants)
119
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.
120Studies Included in the Review of Evidence
Last name first author, 
Publication yearStudy design Country Age 
mean 
(SD)Total 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
121Summary of Studies Reporting Outcome 1: Medically attended 
RSV-associated lower respiratory infection in infants 
Last name 
first author, 
Publication 
yearAge 
mean 
(SD)N 
interventionN 
comparisonComparator 
VaccineAbsolute 
difference/effect 
estimate (99.58% 
CI)Study 
limitations 
(Risk of Bias)
Kampmann B, 
et al.29.0
(5.7)3495 3480 Placebo 17 fewer per 
1,000 (10 to 22 
fewer)None
122Summary of Studies Reporting Outcome 2: Hospitalization for 
RSV-associated lower respiratory tract infection in infants  
Last name first 
author, 
Publication 
yearAge 
mean 
(SD)N 
interventionN 
comparisonComparator 
VaccineAbsolute 
difference/effect 
estimate (99.17% 
CI)Study 
limitations 
(Risk of Bias)
Kampmann B, 
et al.29.0 
(5.7)3495 3480 Placebo 7 fewer per 1,000 
(1 to 10 fewer)None
123Summary of Studies Reporting Outcome 5: RSV -
associated death in infants 
Last name first 
author, 
Publication 
yearAge 
mean 
(SD)N 
interventionN 
comparisonComparator 
VaccineAbsolute 
difference/effe
ct estimateStudy 
limitations 
(Risk of Bias)
Kampmann B, et 
al.29.0
(5.7)3495 3480 Placebo Not estimable 
1 death in a 
placebo 
recipientN/A
Phase 2b RCT, 
unpublished18-49 
(range)114 116 Placebo Not estimable 
0 deaths in trialN/A
124Summary of Studies Reporting Outcome 6: All cause medically 
attended lower respiratory tract infection in infants 
Last name first 
author, 
Publication 
yearAge 
mean 
(SD)N 
interventionN 
comparisonComparator 
VaccineAbsolute 
difference/effect 
estimate (99.17% 
CI)Study 
limitations 
(Risk of Bias)
Kampmann B, et 
al.29.0 
(5.7)3495 3480 Placebo 3 fewer per 1,000 
(22 fewer to 21 
more)None
125Summary of Studies Reporting Outcome 8: Serious 
adverse events in pregnant people 
Last name first 
author, 
Publication 
yearAge 
mean 
(SD)N 
interventionN 
comparisonComparator 
VaccineAbsolute 
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
126Summary of Studies Reporting Outcome 9: 
Reactogenicity (grade 3+) in pregnant people 
Last name first 
author, 
Publication 
yearAge 
mean 
(SD)N 
interventio
nN 
comparisonComparator 
VaccineAbsolute 
difference/effect 
estimateStudy 
limitations 
(Risk of Bias)
Kampmann B, 
et al.29.0 
(5.7)3663 3640 Placebo RR: 0.94 (0.70, 
1.28)None
Phase 2b RCT 27.1
(5.2)114 117 Placebo RR: 0.51 (0.10, 
2.75)None
127Summary of Studies Reporting Outcome 10: Serious 
adverse events in infants 
Last name first 
author, Publication 
yearAge median 
(range)N intervention N comparison Comparator 
VaccineAbsolute 
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
128Summary of Studies Reporting Outcome 11: Preterm 
birth
Last name first 
author, Publication 
yearAge mean 
(SD)N intervention N comparison Comparator 
VaccineAbsolute 
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
129Grade Summary of Findings Table -Benefits
129№ of 
studiesStudy designRisk of 
biasInconsistency Indirectness ImprecisionOther 
considerationsIntervention ComparisonRelative
(95% CI)Absolute
(95% CI)Importance Certainty
Medically attended RSV -associated lower respiratory infection in infants
1 Randomized 
studiesNot serious Not serious Not serious Not serious None 57/3495 (1.6%) 117/3480 
(3.4%)0.487 
(0.332, 
0.706)17 fewer 
per 1,000 
(10 to 22 
fewer)Critical High
23.1% 119 fewer 
per 1,000 
(68 to 154 
fewer)
11.0% 56 fewer 
per 1,000 
(32 to 73 
fewer)
Hospitalizations RSV -associated lower respiratory infection in infants
1 Randomized 
studiesNot serious Not serious Not serious Serious None 19/3495 (0.5%) 44/3480 (1.3%) 0.432 
(0.193, 
0.899)7 fewer per 
1,000 (1 to 
10 fewer)Critical Moderate
1.9% 11 fewer 
per 1,000 (2 
to 15 fewer)
All-cause medically attended lower respiratory infection in infants
1 Randomized 
studiesNot serious Not serious Not serious Serious None 392/3495 
(11.2%)402/3480 
(11.6%)0.97 (0.85, 
1.11)3 fewer per 
1,000 (22 
fewer to 21 
more)Important Moderate
130Grade Summary of Findings Table -Harms
130№ of 
studiesStudy design Risk of biasInconsiste
ncyIndirectness ImprecisionOther 
considerationsIntervention comparisonRelative
(95% CI)Absolute
(95% CI)Importance Certainty
Serious adverse events in pregnant women
2 Randomized 
studiesNot 
seriousNot 
seriousNot serious Serious None 605/3797 
(15.9%)572/3792 
(15.1%)1.06 
(0.95, 
1.17)9 more per 
1,000 (8 
fewer to 26 
more)Critical Moderate
Reactogenicity (3+ or higher) in pregnant women
2 Randomized 
studiesNot 
seriousNot 
seriousSerious Not serious None 85/3777 
(2.3%)87/3757 
(2.3%)0.97 
(0.72, 
1.31)1 fewer per 
1,000 (6 
fewer to 7 
more)Important Moderate
Serious adverse events in infants
2 Randomized 
studiesNot 
seriousNot 
seriousNot serious Serious None 625/3568 
(17.5%)623/3558 
(17.5%)1.01 
(0.91, 
1.11)2 more per 
1,000 (16 
fewer to 19 
more)Critical Moderate
Preterm birth
2 Randomized 
studiesNot 
seriousNot 
seriousNot serious Very 
seriousNone 207/3683 
(5.6%)172/3675 
(4.7%)1.20 
(0.99, 
1.46)9 more per 
1,000 (0 
fewer to 22 
more)Critical Low