Morbidity and Mortality Weekly Report

Use of the Pfizer Respiratory Syncytial Virus Vaccine During Pregnancy for the
Prevention of Respiratory Syncytial Virus–Associated Lower Respiratory Tract
Disease in Infants: Recommendations of the Advisory Committee on
Immunization Practices — United States, 2023
Katherine E. Fleming-Dutra, MD1,*; Jefferson M. Jones, MD1,*; Lauren E. Roper, MPH1; Mila M. Prill, MSPH1; Ismael R. Ortega-Sanchez, PhD1;
Danielle L. Moulia, MPH1; Megan Wallace, DRPH1; Monica Godfrey, MPH1; Karen R. Broder, MD2; Naomi K. Tepper, MD3; Oliver Brooks, MD4;
Pablo J. Sánchez, MD5; Camille N. Kotton, MD6; Barbara E. Mahon, MD1; Sarah S. Long, MD7; Meredith L. McMorrow, MD1

On October 6, 2023, this report was posted as an MMWR Early ≥60 years, contains stabilized prefusion F glycoproteins from
Release on the MMWR website (https://www.cdc.gov/mmwr). RSV A and RSV B and is approved as a single 0.5 mL intramus-
cular dose administered during 32 through 36 weeks’ gestation.
Abstract In clinical trials among pregnant persons at 24–36 weeks’
Respiratory syncytial virus (RSV) is the leading cause of hos- gestation, more preterm births (<37 weeks’ gestation) were
pitalization among U.S. infants. Nirsevimab (Bevfortus, Sanofi observed among RSVpreF vaccine recipients than placebo
and AstraZeneca) is recommended to prevent RSV-associated recipients, although the differences were not statistically
lower respiratory tract infection (LRTI) in infants. In August significant (1,2). Available data were insufficient to establish
2023, the Food and Drug Administration (FDA) approved or exclude a causal relationship between preterm birth and
RSVpreF vaccine (Abrysvo, Pfizer Inc.) for pregnant persons RSVpreF vaccine. FDA labeled the potential risk for preterm
as a single dose during 32–36 completed gestational weeks birth as a warning and approved RSVpreF vaccine for use
(i.e., 32 weeks and zero days’ through 36 weeks and 6 days’ in pregnant persons at 32–36 weeks’ gestation to avoid the
gestation) to prevent RSV-associated lower respiratory tract potential risk for preterm birth at <32 weeks’ gestation, which
disease in infants aged <6 months. Since October 2021, CDC’s is associated with increased risk for morbidity and mortality
Advisory Committee on Immunization Practices (ACIP) (2). More hypertensive disorders of pregnancy were observed
RSV Vaccines Pediatric/Maternal Work Group has reviewed among RSVpreF vaccine recipients compared with placebo
RSV epidemiology and evidence regarding safety, efficacy, recipients, although the differences were not statistically sig-
and potential economic impact of pediatric and maternal nificant. FDA determined that, when RSVpreF is administered
RSV prevention products, including RSVpreF vaccine. On during 32–36 weeks’ gestation, the benefit of vaccination in
September 22, 2023, ACIP and CDC recommended RSVpreF preventing RSV-associated LRTI in infants outweighed risks,
vaccine using seasonal administration (i.e., during September including the potential risk for preterm birth and hypertensive
through end of January in most of the continental United disorders of pregnancy (1,2).
States) for pregnant persons as a one-time dose at 32–36 weeks’ On August 3, 2023, CDC’s Advisory Committee on
gestation for prevention of RSV-associated LRTI in infants Immunization Practices (ACIP) and CDC recommended
aged <6 months. Either maternal RSVpreF vaccination dur- nirsevimab (Beyfortus, Sanofi and AstraZeneca), a long-acting
ing pregnancy or nirsevimab administration to the infant is monoclonal antibody for prevention of severe RSV disease, for
recommended to prevent RSV-associated LRTI among infants, infants aged <8 months who are born during or entering their
but both are not needed for most infants. All infants should first RSV season and for children aged 8–19 months at increased
be protected against RSV-associated LRTI through use of one risk for severe RSV disease entering their second RSV season
of these products. (3). On September 22, 2023, ACIP and CDC recommended
RSVpreF vaccine for pregnant persons as a one-time dose during
Introduction 32–36 completed weeks’ gestation using seasonal administration
In August 2023, the Food and Drug Administration (FDA) (September–January in most of the continental United States)
approved RSVpreF vaccine (Abrysvo, Pfizer Inc.) for pregnant to prevent RSV-associated lower respiratory tract infection
persons to prevent RSV-associated lower respiratory tract dis- (LRTI) in infants. Either maternal RSVpreF vaccination during
ease and severe lower respiratory tract disease in infants aged pregnancy or nirsevimab administration to the infant is recom-
<6 months (1,2). The Pfizer bivalent RSVpreF vaccine, which is mended to prevent RSV-associated LRTI in infants, but both are
the same formulation and dose approved for use in adults aged not needed for most infants. This report describes new recom-
mendations for the use of maternal RSVpreF during pregnancy
* These authors contributed equally to this report.

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 Morbidity and Mortality Weekly Report

and updated clinical guidance regarding the use of nirsevimab 24–36 weeks’ gestation: a phase 2b trial¶ with 581 pregnant
and maternal RSVpreF vaccine. These recommendations will persons (115 of whom received the phase 3 vaccine dose and
be updated as new evidence becomes available. formulation and 117 of whom received placebo) and a phase 3
trial** including 7,392 pregnant persons, randomized 1:1 to
Epidemiology of RSV in U.S. Infants vaccine and placebo arms (15,16). The Work Group used the
RSV is a common cause of LRTI in U.S. infants, most of Grading of Recommendations, Assessment, Development,
whom are infected with RSV during the first year of life (4,5). and Evaluation (GRADE) approach†† to assess the certainty
All infants are at risk for experiencing severe RSV disease. RSV of evidence for outcomes related to maternal RSVpreF vac-
is the leading cause of hospitalization among U.S. infants cination during pregnancy, rated on a scale of very low to
(6); 2% to 3% of young infants will be hospitalized for RSV high certainty. The Work Group employed the Evidence to
disease (7–9). Approximately 58,000–80,000 RSV-associated Recommendation (EtR) Framework§§ to guide its delibera-
hospitalizations and 100–300 RSV-associated deaths occur tions on recommendations for maternal RSVpreF vaccination
annually among U.S. children aged <5 years (10–13). An esti- during pregnancy and review of data on the public health
mated 79% of children aged <2 years hospitalized with RSV problem, benefits and harms, value to the target population,
had no underlying medical conditions (7). RSV-associated acceptability to key stakeholders, feasibility, direct and indirect
hospitalization rates are highest in infants aged <6 months, with resource utilization, and equity.
hospitalization peaking at age 1 month, and then decreasing
with increasing age (7). Vaccine Efficacy and Safety
Before the COVID-19 pandemic, RSV circulation consis- In the Pfizer phase 2b and 3 trials, maternal RSVpreF vac-
tently peaked during winter months in the continental United cination was administered during 24–36 weeks’ gestation
States, although the timing varied by geographic region (14); (15,16). For the GRADE assessment, data were included
however, the COVID-19 pandemic disrupted RSV seasonal- from phase 2b and 3 trials using the trial dosing interval of
ity, with historically low RSV circulation during 2020–21 and 24–36 weeks’ gestation. Using all available data from the trial
early and prolonged circulation during 2021–22 (14). RSV dosing interval provided increased power to detect potential
circulation in 2022–23 began later than during the 2021–22 benefits and harms. Additional analyses of efficacy and safety
season but earlier than prepandemic seasons (14). RSV activ- outcomes from participants who received vaccine or placebo
ity in August and September 2023 suggests that transmission during the approved dosing interval of 32–36 weeks’ gestation
patterns are returning to prepandemic seasonal RSV trends.† were reviewed and are included as a supplement to the evidence
included in GRADE (2,9). The details of the GRADE evidence
Methods profile and supporting evidence for the EtR Framework are
Since October 2021, the ACIP RSV Vaccines Pediatric/ available at https://www.cdc.gov/vaccines/acip/recs/grade/
Maternal Work Group (the Work Group) has met at least pfizer-RSVpreF-pregnant-people.html and https://www.
monthly to review evidence regarding RSV epidemiology and cdc.gov/vaccines/acip/recs/grade/pfizer-RSVpreF-pregnant-
safety, efficacy, and potential economic impact of pediatric people-etr.html.
and maternal RSV prevention products, including RSVpreF
vaccine. A systematic literature search was completed to review Vaccine Efficacy
evidence regarding the efficacy and safety of maternal RSVpreF For the GRADE assessment of benefits, data on vaccine efficacy
vaccination during pregnancy. The Work Group determined among infants from birth through 180 days of life were evalu-
a priori outcomes that were critical or important to vaccine ated (9,16). Efficacy against medically attended RSV-associated
policy decisions.§ Evidence of efficacy and safety were derived LRTI was 51.3% among the full trial population (trial dosing
from multicountry trials that randomized pregnant persons interval of 24–36 weeks’ gestation) and 57.3% when maternal
to receive maternal RSVpreF vaccination or placebo during RSVpreF vaccination was given during the approved dosing
interval (32–36 weeks’ gestation). Efficacy against hospitalization
† https://emergency.cdc.gov/han/2023/han00498.asp; https://www.cdc.gov/
surveillance/nrevss/rsv/index.html ¶ Trial conducted in Argentina, Chile, New Zealand, South Africa, and
§ Critical outcomes: medically attended RSV-associated LRTI in infants,
United States.
hospitalization for RSV-associated LRTI in infants, serious adverse events in ** Trial conducted in Argentina, Australia, Brazil, Canada, Chile, Denmark,
pregnant persons, serious adverse events in infants, and preterm birth Finland, The Gambia, Japan, Mexico, Netherlands, New Zealand, Philippines,
(<37 weeks’ gestation). Important outcomes: intensive care unit (ICU) South Africa, South Korea, Spain, Taiwan, and United States.
admission from RSV hospitalization in infants, mechanical ventilation from †† https://www.cdc.gov/vaccines/acip/recs/grade/about-grade.html
RSV hospitalization in infants, RSV-associated death in infants, all-cause §§ https://www.cdc.gov/vaccines/acip/recs/grade/downloads/acip-evidence-recs-
medically attended LRTI in infants, all-cause hospitalization for LRTI in infants, framework.pdf
and reactogenicity (grade 3 or higher) in pregnant persons.

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 Morbidity and Mortality Weekly Report

for RSV-associated LRTI was 56.8% during the full trial dosing maternal RSVpreF vaccination at 32–36 weeks’ gestation to
interval and 48.2% during the approved dosing interval (Table 1). outweigh the potential risks for preterm birth and hypertensive
disorders of pregnancy.
Vaccine Safety The most common local and systemic adverse reactions
For the GRADE assessment of harms, results from the phase were pain at the injection site, headache, muscle pain, and
2b and phase 3 trials were pooled¶¶ (9,16). The overall evidence nausea.††† Although not statistically significant, in the full trial
certainty using GRADE criteria was rated as very low, driven population more preterm births and hypertensive disorders of
by the uncertainty in the critical harm outcome of preterm pregnancy (including preeclampsia) were observed in persons
birth (<37 weeks’ gestation).*** ACIP judged the benefits of administered the vaccine rather than the placebo, and more
infants whose mothers received the vaccine had low birth-
¶¶ A serious adverse event is defined as any untoward medical occurrence that weight ≤5.5 lbs (≤2,500 g) and neonatal jaundice compared
results in death, is life-threatening, requires inpatient hospitalization or
prolongation of existing hospitalization, results in persistent disability or
with infants whose mothers received the placebo.§§§ Pregnant
incapacity, or is a congenital anomaly or birth defect. Serious adverse events persons at increased risk for preterm delivery were excluded
in pregnant persons were collected ≤6 months after delivery. Serious adverse from the phase 2b and phase 3 trials. In the full trial population,
events in infants were collected ≤12 months after delivery. Reactogenicity
events were collected ≤7 days following injection. preeclampsia occurred among 1.8% (95% CI = 1.4%–2.3%)
*** The outcome of preterm birth was rated as very low certainty. Very serious †††
concern for imprecision was noted because of the CI range containing estimates In the phase 3 trial among 3,663 RSVpreF recipients and 3,638 to 3,639
for which different policy decisions might be considered as well as not meeting placebo recipients, injection site pain was reported by 40.6% of RSVpreF
optimum information requirements. In addition, serious concern for and 10.1% of placebo recipients; headache by 31.0% of RSVpreF and 27.6%
indirectness was present as 55% of participants in the phase 3 trial and 62% of placebo recipients; muscle pain by 26.5% of RSVpreF and 17.1% placebo
of participants in the phase 2b trial did not receive vaccine or placebo in the recipients; and nausea by 20.0% of RSVpreF and 19.2% of placebo recipients.
§§§ Low birthweight ≤5.5 lbs (≤2,500 g) and neonatal jaundice are more common
approved dosing interval (32–36 weeks’ gestation). In the approved dosing
interval, there is less opportunity for serious adverse events, including preterm among infants born preterm than among infants born at term. https://www.
birth, compared with the trial dosing interval (24–36 weeks’ gestation). marchofdimes.org/find-support/topics/birth/premature-babies

TABLE 1. Effect estimates for the Pfizer maternal RSVpreF vaccine for the trial dosing interval and the approved dosing interval
VE or RR (CI)*
Trial dosing interval Approved dosing interval
Outcome (24–36 weeks’ gestation)† (32–36 weeks’ gestation)§
Benefits (efficacy against outcome), (VE) assessed at age 0–180 days
Medically attended RSV-associated LRTI in infants 51.3 (29.4 to 66.8)¶ 57.3 (29.8 to 74.7)
Severe medically attended RSV-associated LRTI in infants** 69.4 (44.3 to 84.1)¶ 76.5 (41.3 to 92.1)
Hospitalization for RSV-associated LRTI 56.8 (10.1 to 80.7)†† 48.2 (–22.9 to 79.6)
Intensive care unit admission from RSV hospitalization in infants 42.9 (–124.8 to 87.7) One event in the vaccine group
Two events in the placebo group
Mechanical ventilation from RSV hospitalization in infants 100 (–9.1 to 100) Zero events in the vaccine group
Two events in the placebo group
All-cause medically attended LRTI in infants 2.5 (–17.9 to 19.4)†† 7.3 (–15.7 to 25.7)
All-cause hospitalization for LRTI in infants 28.9 (–2.0 to 50.8) 34.7 (–18.8 to 64.9)
Harms (RR)§§
Serious adverse events in pregnant persons¶¶ 1.06 (0.95 to 1.17) 1.02 (0.87 to 1.20)
Reactogenicity (grade 3 or higher systemic reactions) in pregnant persons*** 0.97 (0.72 to 1.31) 0.98 (0.62 to 1.54)
Serious adverse events in infants††† 1.01 (0.91 to 1.11) 1.04 (0.90 to 1.20)
Preterm birth (<37 weeks’ gestational age) 1.20 (0.99 to 1.46) 1.15 (0.82 to 1.61)
Abbreviations: GRADE = Grading of Recommendations, Assessments, Development, and Evaluations; LRTI = lower respiratory tract infection; RR = relative risk;
RSV = respiratory syncytial virus; VE = vaccine efficacy.
* 95% CI unless otherwise noted. When 95% CI not used, the CI was adjusted using the Bonferroni procedure, accounting for the primary endpoints’ results.
† Vaccine efficacy was calculated as (1 – [P / (1 – P)]) x 100%, where P is the number of cases in the RSVpreF group divided by the total number of cases.
§ Vaccine efficacy was calculated as (1 − [hP / (1 − P)]) x 100%, where P is the number of cases in the RSVpreF group divided by the total number of cases and h is
the ratio of number of participants at risk in the placebo group to the number of participants at risk in the RSVpreF group.
¶ 97.58% CI.
** Severe medically attended RSV-associated LRTI was a co-primary endpoint of the phase 3 clinical trial. This outcome was not included by CDC’s Advisory Committee
on Immunization Practices RSV Vaccines Pediatric/Maternal Work Group as an a priori GRADE outcome critical or important to vaccine policy decision making.
†† 99.17% CI.
§§ Pooled RR estimates were independently calculated using counts of events and participants in the phase 3 trial interim analysis and phase 2b trial among those
who received the phase 3 vaccine formulation.
¶¶ Serious adverse events in pregnant persons were collected through 6 months after delivery.
*** Up to 7 days after injection. When selecting the a priori harm outcomes, CDC’s Advisory Committee on Immunization Practices RSV Vaccines Pediatric/Maternal
Work Group defined reactogenicity as both local and systemic reactions. These data only reflect systemic reactions.
††† Serious adverse events in infants were collected through 6 months after delivery.

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 Morbidity and Mortality Weekly Report

of vaccine recipients and in 1.4% (95% CI = 1.1%–1.9%) inflammatory neurologic events (two cases of Guillain-Barré
of placebo recipients (2). Pregnancy-related serious adverse syndrome, including one case of the Miller-Fisher variant, and
events overall (which include preeclampsia) occurred in 16.2% one case of undifferentiated motor-sensory polyneuropathy)
(95% CI = 15.1%–17.5%) of participants in the vaccine were reported within 42 days after vaccination among 20,255
group and 15.2% (95% CI = 14.0%–16.4%) in the placebo investigational vaccine recipients aged ≥60 years, whereas no
group¶¶¶ (2). cases were observed among placebo recipients (17). No cases
The data reviewed by ACIP support that limiting vaccine of Guillain-Barré syndrome or other inflammatory neurologic
administration to the approved dosing interval (32–36 weeks’ events were reported in the phase 2b or phase 3 trials among
gestation) reduces the potential risk for preterm birth and pregnant persons (15).
thereby, the potential for related complications compared with
the trial dosing interval of 24–36 weeks’ gestation. In the Pfizer Economic Analysis
phase 3 trial, using the full trial dosing interval, 5.7% of infants ACIP considered whether use of RSVpreF vaccine in
born to RSVpreF vaccine recipients were preterm compared pregnant persons is a reasonable and efficient allocation of
with 4.7% of those born to placebo recipients (Table 2). In resources. The societal incremental cost effectiveness ratio for
the full trial population, more than one half of preterm births RSVpreF vaccine, assuming year-round dosing and cost of
occurred >30 days after vaccination (121 [60%] of 201 preterm $295 per dose, was $400,304 per quality-adjusted life year
births in the vaccine group and 98 [58%] of 169 preterm births (QALY) saved. Assuming a pre–COVID-19 typical RSV sea-
in the placebo group), and most preterm births occurred at or sonality in most of the continental United States, the societal
after 33 weeks’ gestation (194 [97%] of 201 preterm births in incremental cost effectiveness ratio for administering RSVpreF
the vaccine group versus 161 [95%] of 169 preterm births in to pregnant persons during September–January would be
the placebo group). When the prevalence of preterm birth was $167,280/QALY saved (9).
assessed among phase 3 trial participants who received vaccine
during the approved dosing interval (32–36 weeks’ gestation), Recommendations for Use of RSVpreF Vaccine in
4.2% of infants were born preterm in the vaccine group Pregnant Persons
versus 3.7% in the placebo group. The majority of preterm On September 22, 2023, ACIP and CDC recommended
births among participants who received vaccination during maternal Pfizer RSVpreF vaccination in pregnant persons as a
the approved dosing interval occurred at 36 weeks’ gestation one-time dose at 32 weeks and zero days’–36 weeks and 6 days’
(49 [72%] of 68 preterm births in the vaccine group and 35 gestation using seasonal administration (meaning September–
[59%] of 59 preterm births in the placebo group). January in most of the continental United States) for preven-
The Pfizer maternal RSVpreF vaccine is the same formula- tion of RSV-associated LRTI in infants aged <6 months.****
tion and dose approved for use in adults aged ≥60 years. In clin- These recommendations will be updated as new evidence
ical trials in adults aged ≥60 years for RSVpreF vaccine, three becomes available.
¶¶¶ Among the full trial population, gestational hypertension occurred in 1.1% **** On September 22, 2023, ACIP voted 11–1 in favor of the recommendation:
(95% CI = 0.8%–1.5%) of vaccine recipients and 1.0% (95% CI = 0.7%–1.4%) maternal RSV vaccine is recommended for pregnant persons during
of placebo recipients. Hypertension occurred in 0.4% (95% CI = 0.2%–0.6%) 32–36 weeks’ gestation, using seasonal administration, to prevent RSV-
of vaccine recipients and 0.2% (95% CI = 0.1%–0.4%) of placebo recipients. associated LRTI in infants.

TABLE 2. Preterm birth (<37 weeks’ gestation), low birthweight and neonatal jaundice outcomes in Pfizer RSVpreF vaccine phase 3 trial for the
trial dosing interval and the approved dosing interval*
Group, trial dosing interval Group, approved dosing interval
(24–36 wks’ gestation)† (32–36 wks’ gestation)§
RSVpreF Placebo RSVpreF Placebo
N = 3,568 N = 3,558 N = 1,628 N = 1,604
Outcome No. % (95% CI) No. % (95% CI) No. % (95% CI) No. % (95% CI)
Preterm birth¶ 202 5.7 (4.9–6.5) 169 4.7 (4.1–5.5) 68 4.2 (3.3–5.3) 59 3.7 (2.8–4.7)
Low birthweight** 181 5.1 (4.4–5.8) 155 4.4 (3.7–5.1) 67 4.1 (3.2–5.2) 54 3.4 (2.5–4.4)
Neonatal jaundice 257 7.2 (6.4–8.1) 240 6.7 (5.9–7.6) 102 6.3 (5.1–7.6) 107 6.7 (5.5–8.0)
* All differences between vaccine group and placebo group were not statistically significant, as determined by nonoverlapping CIs.
† https://www.fda.gov/media/168889/download?attachment
§ Data obtained directly from the sponsor during August, 2023.
¶ Less than 37 weeks’ gestation.
** Less than ≤5.5 lbs (2,500 g).

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 Morbidity and Mortality Weekly Report

Clinical Guidance in infants, but administration of both products is not needed

Seasonal Administration of RSVpreF Vaccine. Maternal for most infants. Providers who care for pregnant persons
RSVpreF vaccine should be administered to pregnant persons should discuss the relative advantages and disadvantages of both
during September–January in most of the continental United maternal RSVpreF vaccination and nirsevimab and consider
States to target vaccine to pregnant persons whose infants patient preferences when determining whether to vaccinate the
will be in their first months of life, when protection from pregnant person or to rely on administration of nirsevimab to
maternal vaccination would be at its highest, during the RSV the infant (Box) (19).
season. Administering maternal RSVpreF vaccine starting in No data are available directly comparing the efficacy of
September (1–2 months before the anticipated start of the nirsevimab and maternal RSVpreF vaccine in preventing
RSV season) and continuing through January (2–3 months RSV-associated LRTI in infants. Protection conferred through
before the anticipated end of the RSV season) will maximize maternal vaccination will likely wane after 3 months, as has
cost-effectiveness and benefits. In jurisdictions with RSV sea- been observed in infants born to pregnant persons who have
sonality that differs from most of the continental United States, received influenza and COVID-19 vaccines (16,20,21).
including Alaska, southern Florida, Guam, Hawaii, Puerto However, because maternal RSV vaccination at 32–36 weeks’
Rico, U.S.-affiliated Pacific Islands, and U.S. Virgin Islands, gestation is recommended during only September–January
providers should follow state, local, or territorial guidance on in most of the continental United States, most infants of
timing of maternal RSVpreF vaccination.††††
Simultaneous Administration with Other Vaccines. In BOX. Relative advantages and disadvantages of maternal RSVpreF
vaccination and nirsevimab administration to infants to prevent
accordance with CDC’s General Best Practices Guidelines for respiratory syncytial virus lower respiratory tract infection in
Immunization, maternal RSVpreF vaccine can be administered infants — United States, 2023
to pregnant persons with other recommended vaccines, such
as tetanus, diphtheria, and pertussis (Tdap), influenza, and Maternal RSVpreF vaccination
COVID-19 vaccines, without regard to timing, including Advantages
simultaneous vaccination at different anatomic sites on the • Provides protection immediately after birth
same day (18). • Might be more resistant to potential mutations in
Additional Vaccine Doses in Subsequent Pregnancies. F protein*
Currently, no data are available on either the efficacy of the first Disadvantages
lifetime dose to protect infants born after subsequent pregnan- • Protection potentially reduced if fewer antibodies are
cies or the safety of additional doses given during subsequent produced or are transferred from pregnant person to
pregnancies. Additional data are needed to determine whether baby (e.g., pregnant person is immunocompromised
additional seasonal doses during subsequent pregnancies are or infant born soon after vaccination)
indicated, and ACIP might update recommendations in the • Potential risk for preterm birth and hypertensive
future, as data become available. disorders of pregnancy
Infant nirsevimab administration
Updated Clinical Guidance for Use of Nirsevimab and Advantages
Maternal RSVpreF Vaccine • Studies of antibody levels suggest that protection
Recommendations for nirsevimab, a long-acting monoclo- might wane more slowly than protection from the
nal antibody product, have been previously published (3). maternal RSV vaccine
Either maternal RSVpreF vaccination during pregnancy at • Assures direct receipt of antibodies rather than relying
32–36 weeks’ gestation or nirsevimab immunization for infants on transplacental transfer
aged <8 months who are born during or are entering their first • No risk for adverse pregnancy outcomes
RSV season is recommended to prevent RSV-associated LRTI Disadvantages
• Potentially limited availability during 2023–24
†††† The timing of maternal RSVpreF vaccination might vary in these
jurisdictions because the historic timing of RSV circulation differs from
RSV season
the rest of the United States. As maternal RSVpreF vaccination should start • Requires infant injection
1–2 months before the anticipated start of the RSV season and continue
through 2–3 months before the anticipated end of the RSV season, it is
not feasible to change maternal RSVpreF vaccination timing based on Abbreviation: RSV = respiratory syncytial virus.
year-to-year variations in RSV circulation. Thus, in most of the continental * Maternal RSV vaccination results in a polyclonal immune response, which
United States, maternal RSVpreF vaccination should be given in is expected to be more resistant to potential mutations in the RSV
September–January, regardless of year-to-year variation in RSV circulation. F protein than a monoclonal antibody product.

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 Morbidity and Mortality Weekly Report

vaccinated mothers will be born during an RSV season.

Summary
Mothers of most infants born outside of RSV season (i.e., dur-
What is already known about this topic?
ing April–September) will not have been vaccinated; therefore,
nirsevimab is recommended for these infants at the onset of Nirsevimab is recommended in infants to prevent respiratory
syncytial virus (RSV)-associated lower respiratory tract infection
the RSV season if they are aged <8 months. (LRTI). In August 2023, the Food and Drug Administration
At least 14 days are likely needed after maternal vaccination for approved Pfizer RSV vaccine for pregnant persons at
development and transplacental transfer of maternal antibodies 32–36 weeks’ gestation to prevent RSV-associated LRTI in
to protect the infant (16,22); therefore, nirsevimab is recom- infants aged <6 months.
mended for infants born <14 days after maternal RSVpreF vac- What is added by this report?
cination. The earliest an infant could be born and be considered On September 22, 2023, CDC’s Advisory Committee on
protected by maternal receipt of RSVpreF vaccine at 32 weeks’ Immunization Practices recommended RSV vaccine for
gestation (the earliest recommended time for vaccination) would pregnant persons at 32–36 weeks’ gestation using seasonal
be at 34 gestational weeks. Therefore, nirsevimab is recom- administration (meaning September–January in most of the
United States) to prevent RSV-associated LRTI in infants aged
mended for all infants born at <34 weeks’ gestation. <6 months.
Nirsevimab is recommended for infants aged <8 months
What are the implications for public health practice?
born during or entering their first RSV season whose mother
CDC recommends protecting all infants against RSV-associated
did not receive RSVpreF vaccine, whose mother’s receipt of
LRTI through use of either the maternal RSV vaccine or infant
RSVpreF vaccine is unknown, or who were born <14 days receipt of nirsevimab.
after maternal vaccination. Nirsevimab is not needed for most
infants aged <8 months whose mother received RSVpreF vac-
Precautions and Contraindications
cine ≥14 days before birth. Nirsevimab may be considered for
infants born to vaccinated mothers in rare circumstances when, As with all vaccines, RSV vaccination should be delayed for
based on the clinical judgment of the health care provider, the persons experiencing moderate or severe acute illness with or
potential incremental benefit of administration is warranted. without fever (precaution). RSV vaccines are contraindicated
These situations include, but are not limited to, infants born for and should not be administered to persons with a history of
to mothers who might not have mounted an adequate immune severe allergic reaction, such as anaphylaxis, to any component
response to vaccination (e.g., persons with immunocompro- of the vaccine.
mising conditions) or who have conditions associated with
Reporting of Vaccine Adverse Events
reduced transplacental antibody transfer (e.g., persons living
with HIV infection) (23); infants who might have experienced Adverse events after vaccination should be reported to the
loss of maternal antibodies, such as those who have undergone Vaccine Adverse Event Reporting System (VAERS). Reporting
cardiopulmonary bypass (24) or extracorporeal membrane is encouraged for any clinically significant adverse event
oxygenation; and infants with substantially increased risk for even if it is uncertain whether the vaccine caused the event.
severe RSV disease (e.g., hemodynamically significant congeni- Information on how to submit a report to VAERS is avail-
tal heart disease, or intensive care admission requiring oxygen able at https://vaers.hhs.gov/index.html or by telephone at
at hospital discharge). 1-800-822-7967.
Infants and children aged 8–19 months who are at increased
Future Research and Monitoring Priorities
risk for severe RSV disease and are entering their second RSV
CDC will monitor adverse events, including preterm birth,
season are recommended to receive nirsevimab regardless of
hypertensive disorders of pregnancy, and inflammatory neu-
maternal RSVpreF vaccination (3). Recommendations for
rologic events after RSVpreF vaccination in pregnant persons
timing of nirsevimab administration, coadministration of nir-
through VAERS and the Vaccine Safety Datalink (https://www.
sevimab with routine childhood vaccines, reporting of adverse
cdc.gov/vaccinesafety/ensuringsafety/monitoring/vsd/index.
events, and recommendations for use for infants and children
html). Reactions and health impacts after RSVpreF vaccina-
aged 8–19 months who are at increased risk for severe RSV
tion will also be monitored through v-safe. According to FDA
disease and who are entering their second RSV season have
post-marketing requirements, the manufacturer will conduct
been previously published and remain unchanged (3).
post-marketing studies to assess preterm birth and hypertensive
disorders of pregnancy, including preeclampsia (25).

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 Morbidity and Mortality Weekly Report

Acknowledgments Taylor, Naomi Tepper, Natalie Thornburg, Megan Wallace, Denis

Voting members of the Advisory Committee on Immunization Wang, Melinda Wharton, Raigan Wheeler, Amber Winn, Patricia
Practices (in addition to listed authors): Lynn Bahta, Minnesota (Akpobome) Wodi.
Department of Health; Beth P. Bell, University of Washington; Corresponding author: Katherine E. Fleming-Dutra, [email protected].
Wilbur H. Chen, University of Maryland School of Medicine; 1Coronavirus and Other Respiratory Viruses Division, National Center for
Sybil Cineas, Warren Alpert Medical School of Brown University; Immunization and Respiratory Diseases, CDC; 2Immunization Safety Office,
Matthew F. Daley, Kaiser Permanente Colorado; Grace M. Lee, National Center for Emerging and Zoonotic Infectious Diseases, CDC;
3Division of Reproductive Health, National Center for Chronic Disease
Stanford University School of Medicine; Jamie Loehr, Cayuga
Prevention and Health Promotion, CDC; 4Watts Healthcare Corporation, Los
Family Medicine; Veronica V. McNally, Franny Strong Foundation; Angeles, California; 5The Research Institute at Nationwide Children’s Hospital,
Katherine A. Poehling, Wake Forest School of Medicine. The Ohio State University College of Medicine, Columbus, Ohio; 6Harvard
Medical School, Boston, Massachusetts; 7Drexel University College of Medicine,
ACIP Pediatric/Maternal RSV Work Group Philadelphia, Pennsylvania.

Chair: Sarah S. Long, Drexel University College of Medicine; All authors and work group members have completed and
ACIP Members: Oliver Brooks, Watts Healthcare Corporation; submitted the International Committee of Medical Journal Editors
Camille N. Kotton, Harvard Medical School; Pablo J. Sánchez, form for disclosure of potential conflicts of interest. No potential
The Research Institute at Nationwide Children’s Hospital; conflicts of interest were disclosed.
Consultants: Kevin Ault, Western Michigan University; Carol
Baker, McGovern Medical School, University of Texas Health References
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