Document text
Maternal/Pediatric RSV Work Group Considerations
CDR Jefferson Jones, MD MPH FAAP, USPHS
Co-lead, Respiratory Syncytial Virus Vaccines – Maternal/Pediatric
Work Group
Coronavirus and Other Respiratory Viruses Division
ACIP General Meeting
June 28, 2024National Center for Immunization and Respiratory Diseases
•Anticipated supply of maternal RSV vaccine and nirsevimab
•Updates on post -introduction nirsevimab and maternal RSV vaccine safety
and effectiveness monitoring
•Revaccination of pregnant people during subsequent pregnanciesOutline
•For maternal RSV vaccine, no anticipated supply/demand mismatch
•For nirsevimab, limited availability beginning early September, ramping up
during September, broadly available by October 1
•Original ACIP recommendations (as published in MMWR ) apply for 2024 -
25 RSV season
•All infants are recommended to be protected by either maternal RSV
vaccination or nirsevimab for the 2024 -25 RSV seasonAnticipated supply of maternal RSV vaccine and
nirsevimab for 2024 –2025 RSV season
Updates on post -introduction nirsevimab and
maternal RSV vaccine safety and effectiveness
monitoring
•Among reports received in VAERS after maternal Pfizer RSV vaccine, the
most frequent adverse events reported were local and systemic symptoms
(e.g., headache) and pregnancy specific conditions (e.g., preterm delivery)
-Expected for a vaccine recommended for pregnant persons at 32 -36 weeks’
gestation
-No verified reports of Guillain Barré syndrome
•Preliminary findings in the Vaccine Safety Datalink (VSD) suggest that the
incidence of preterm births is 4.1% among pregnant persons who received
Pfizer RSV vaccine during the 2023 -2024 respiratory season
-Within VSD’s expected historical range of the incidence of preterm births at 32 -36
weeks’ gestation (3.1–6.1%) before introduction of this vaccine
-Matched analysis for preterm birth and other safety outcomes is in progressMaternal RSV vaccine safety
The Vaccine Adverse Event Reporting System (VAERS)
Vaccine Safety Datalink (VSD) | CDC
•Suspected adverse reactions after nirsevimab administration are
recommended to be reported to MedWatch
-These reports are entered into the FDA Adverse Event Reporting System (FAERS)
database
•If administered on the same day as a vaccine, suspected adverse reactions
after nirsevimab are reported to VAERS
-FDA/CDER reviewers review these VAERS reports
•Similar to VAERS, an incidence of an adverse event cannot be determined
from voluntary reportingNirsevimab adverse event reporting
FDA Adverse Event Reporting System (FAERS) Public Dashboard | FDA
•The most frequently reported adverse events involved patients who
reportedly developed breakthrough RSV infections despite receiving
nirsevimab, and included signs, symptoms, or complications of these
infections (e.g., bronchiolitis)
•Cases of serious hypersensitivity reactions with nirsevimab were identified
in the post -marketing setting and the product labeling was updated in
February 2024
-Serious hypersensitivity reactions have been reported following BEYFORTUS
administration. These reactions included urticaria, dyspnea, cyanosis, and/or
hypotonia.
•No additional safety signals have been identified at this timeSummary of nirsevimab post -marketing adverse
events reported to FAERS and VAERS
FDA Adverse Event Reporting System (FAERS) Public Dashboard | FDA
•Safety data on nirsevimab and maternal RSV vaccine are reassuring, but
population -based studies with comparison groups are needed and pending
•Because of U.S. recommendation that Pfizer maternal RSV vaccine be given
at 32 –36 weeks gestation, unlikely to accumulate U.S. data on safety of
vaccine given at 24 –31 weeks gestation
•Hypersensitivity reactions in young infants are rare and can be difficult to
discern from startle reactions or vasovagal reactions1WG considerations on safety
1Agrabenhenrich et al. 2016 J Allergy Clin Immunol
•Effectiveness against RSV -associated hospitalization was 91% in NVSN and
98% in VISION
•Effectiveness against any medically attended RSV -associated ARI episode
in NVSN was 89%, and effectiveness against RSV -associated ED visits was
77% in VISION
•CDC platform estimates are consistent with studies in Europe,1
•Longer follow up time needed to determine duration of protection
•Limited impact on RSV hospitalization burden, likely because of late
administration
-Substantial decreases in RSV -associated hospitalizations in young infants reported
in Spain, Luxembourg, and Italy with early implementation and high coverage2Nirsevimab effectiveness
1 Consolati Vaccine 2024 ; Ezpeleta Vaccine 2024 ; Lopez -Lacort Eurosurveillance 2024 ; Ares -Gomez Lancet Inf Dis 2024; Coma SSRN preprint 2024 ;
2Ernst Eurosurveillance 2024 ; Consolati Vaccine 2024 ; Mazagatos Influenza Other Respir Viruses 2024
•Unable to estimate maternal RSV vaccine effectiveness during the 2023 -24
season due to
-Limited uptake of maternal RSV vaccine
-Early onset of the 2023 -2024 RSV season
-Timing of vaccine rollout
•CDC will continue to monitor maternal RSV vaccine effectiveness in future
seasonsMaternal RSV vaccine effectiveness
•Evidence shows nirsevimab to be highly effective
•Duration of protection from nirsevimab and maternal vaccination remains
unknown
•Important studies are needed for 2024 -25 season and future RSV seasons
-Maternal vaccine effectiveness
-Nirsevimab effectiveness with longer follow up time, which should be available
with earlier widespread availability
-Nirsevimab effectiveness among children aged 8 –19 months with increased risk
for severe disease during their second RSV season
-Impact on RSV burden when nirsevimab and maternal vaccine are given with
earlier administration and potentially increased uptakeWG considerations on effectiveness
Revaccination of pregnant people during
subsequent pregnancies
•ACIP recommendations for Pfizer RSV maternal vaccine state that
-Currently, no data are available on either the efficacy of the first lifetime dose to
protect infants born after subsequent pregnancies or the safety of additional
doses given during subsequent pregnancies. Additional data are needed to
determine whether additional seasonal doses during subsequent pregnancies are
indicated, and ACIP might update recommendations in the future, as data become
available.
•Still no data on additional RSV vaccine doses in subsequent pregnancies
•There are potentially people who received an RSV vaccine during
pregnancy for the 2023 -24 RSV season who could have a subsequent
pregnancy during the 2024 -2025 RSV seasonAdditional RSV vaccine doses in subsequent
pregnancies
Pfizer ABRSYSVO vaccine efficacy against primary clinical trial
outcomes over time among adults aged ≥60 years
Vaccine Primary outcomeEfficacy (95% CI),
months 0 –12aEfficacy (95% CI),
months 13 –24a
Pfizer ABRYSVORSV LRTI with ≥2 lower
respiratory sx62% (41, 76)
Median 12 months follow -up per
participant55% (26, 73)
Median 6 months follow -up per
participant
RSV LRTI with ≥3 lower
respiratory sx86% (63, 96)
Median 12 months follow -up per
participant74% (27, 92)
Median 6 months follow -up per
participant
Abbreviations: CI: confidence interval, LRTI: lower respiratory tract illness, sx: signs or symptoms, LRTD: lower respiratory tract disease
a.Nominal 12 -month efficacy. Not all trial participants contributing to each estimate had 12 months’ follow up time. Median per -
participant follow -up time is reported below each estimate.
•Antibody titer lower following 2nd dose at 12 months than initial response
•Antibody titer prior to 2nd dose above baselinePfizer RSV vaccine Phase 1/2 immunogenicity results in
nonpregnant adults
J Infect Dis , jiae185, https://doi.org/10.1093/infdis/jiae185
•ACIP Tdap recommendations state that "When ACIP considered
recommending Tdap vaccination during each pregnancy, the safety
information concerning booster doses of Tdap in pregnant women
previously vaccinated with Tdap was not available"
•"ACIP recognized the need for safety studies of severe adverse events
when Tdap is administered during subsequent pregnancies but concluded
that the potential benefit of preventing pertussis morbidity and mortality
in infants too young to be fully vaccinated outweighs the theoretical
concern of possible localized severe adverse events in pregnant women
receiving Tdap. ACIP also concluded that experience with tetanus toxoid –
containing vaccines suggests no excess risk for severe adverse events
among women receiving Tdap with each pregnancy."Tdap recommended during each pregnancy
Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committe e on Immunization Practices
(ACIP) | MMWR (cdc.gov)
Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine (Tdap) in Pregn ant Women — Advisory
Committee on Immunization Practices (ACIP), 2012 (cdc.gov)
•Concerning that data in older adults suggest revaccination does not
restore antibody levels to those after first dose
-Antibody levels are particularly important for maternal vaccination since infants
are protected through transplacental transfer of antibodies
•RSV vaccine differs from Tdap vaccine
-Maternal RSV vaccine has a potential safety concern for preterm birth and
hypertensive disorders of pregnancy
-Alternative product, nirsevimab, exists that can protect infants from severe RSV
for subsequent pregnanciesWG consideration on additional RSV vaccine doses in
subsequent pregnancies
https://www.cdc.gov/mmwr/volumes/72/wr/mm7241e1.htm
•Additional data are needed prior to recommending RSV vaccine during
each pregnancy (i.e., during subsequent pregnancies)
-Antibody data in pregnant people and infants with vaccination during subsequent
pregnancies
-Safety data (e.g., reactogenicity) with vaccination during subsequent pregnancies
-Safety data of RSV vaccine during the first pregnancy it is administered,
particularly regarding outcomes of preterm birth and hypertensive disorders of
pregnancyWG considerations for needed data to make RSV vaccine
recommendations during subsequent pregnancies
•People who received a maternal RSV vaccine during a previous pregnancy
are not recommended to receive additional doses during future
pregnancies
•Infants born to people who were vaccinated only during a prior pregnancy
should receive nirsevimab
•Recommendations can be updated in the future if additional data are
availableRecommendations for additional RSV vaccine doses in
subsequent pregnancies
https://www.cdc.gov/mmwr/volumes/72/wr/mm7241e1.htm
For more information, contact CDC
1-800-CDC-INFO (232 -4636)
TTY: 1 -888-232-6348 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.