Counsel Patients Who Have Questions About Maternal RSV Immunizations

Respiratory syncytial virus (RSV) causes lower respiratory tract infections (LRTIs) that result in an estimated 58,000 to 80,000 hospitalizations per year in US children under the age of 5 years.¹ Infants younger than 12 months of age are at increased risk for severe hospitalizations and death. Certain disease states including prematurity (defined as infants born before 29 weeks’ gestation), chronic lung disease, and hemodynamically significant congenital heart failure place infants at an even greater risk, but the majority of RSV hospitalizations occur in otherwise healthy infants.²

Vaccination during pregnancy is a routine practice to protect both mother and fetus from severe illness.³ Table 1^3-5 lists current Advisory Committee on Immunization Practices (ACIP) recommendations. Much like the timing of the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, RSV vaccination is reserved for the third trimester to trigger additional maternal antibody production against RSV and provide passive immunity to the fetus before birth. RSVpreF (Abrysvo; Pfizer) is currently the only FDA-approved RSV vaccine for pregnant patients between 32 and 36 weeks’ gestation.⁵

AVAILABLE RSV VACCINES

RSVpreF is a bivalent recombinant intramuscular vaccine approved for maternal vaccination to protect infants against RSV-associated LRTIs. It is the same formulation approved for use in patients 60 years and older. When administered 14 days or more prior to delivery, RSVpreF provides infants up to 6 months of protection against RSV-associated LRTI.⁶ Unlike inactivated influenza vaccines, which are given interchangeably in practice based on manufacturer availability, RSV vaccines are notinterchangeable. Adjuvanted RSVpreF3 (Arexvy; GSK) and mRNA-1345 (mRESVIA; Moderna) are approved for use in patients 60 years and older and are not approved for use during pregnancy.⁷

SAFETY AND EFFICACY OF RSV VACCINES IN PREGNANCY

In the MATISSE trial (NCT04424316), researchers examined the safety and efficacy of RSVpreF in preventing medically attended severe RSV-associated LRTIs in infants. The trial was a phase 3, double-blind trial that followed infants for 1 to 2 years. It included pregnant women at 24 to 36 weeks’ gestation who were aged 49 years or younger with an uncomplicated pregnancy. In total, 7392 women received treatment randomized to either RSVpreF (3682) or placebo (3578). The primary end points were severe RSV-associated LRTI and LRTI in infants after birth at 90, 120, 150, and 180 days.⁸

A total of 3570 infants were born to women who received RSVpreF and 3558 to those who received placebo. Demographics were similar among both groups, with a median age of 29 and median gestation of 31.3 weeks.

In the RSVpreF group, a total of 53 severe RSV-associated LRTIs were detected vs 196 in the placebo group. Vaccine efficacy was 69.4% (97.58% CI, 44.3-84.1). Within 180 days after birth, 57 infants of mothers in the vaccine group and 117 of those in the placebo group had RSV illness, showing a vaccine efficacy of 51.3% (97.8% CI, 29.4-66.8).⁸

Local reactions were reported in 41% of patients who received RSVpreF vs 10% who received placebo. Other adverse effects (AEs) included muscle pain (27% vs 17%, respectively) and headache (31% vs 28%). A total of 17 deaths occurred from birth through 24 months of age: 5 in the vaccine group and 12 in the placebo group.⁸ When reviewing safety data, investigators determined there were insufficient data to show a causal relationship between RSVpreF and preterm birth (defined as less than 37 weeks).⁸ However, because preterm birth was higher in the treatment group, the FDA placed a warning in the package insert and approved RSVpreF’s use starting at 32 weeks’ gestation.^5,6,8

Researchers also investigated adjuvanted RSVpreF3 in a phase 3, randomized, placebo-controlled trial with the goal of gaining approval for its use in pregnant patients to protect infants from RSV infection. The trial was halted early after investigators began to analyze safety data and discovered the treatment group had an increased incidence of preterm birth.⁹

Moderna is now enrolling pregnant patients in a phase 2 clinical trial investigating the safety and efficacy of an RSV vaccine that uses mRNA technology.¹⁰ Furthermore, on May 31, Moderna received FDA approval for its mRNA RSV vaccine to protect adults aged 60 years and older from lower respiratory tract disease caused by RSV infection,¹¹ clearing the way for potential future RNA-based immunizations.

MATERNAL RSV VACCINATION RECOMMENDATIONS

ACIP recommends that pregnant patients receive the RSVpreF vaccine between 32 and 36 weeks’ gestation.⁵ RSVpreF is supplied in a vial containing the lyophilized antigen component and either a prefilled syringe or a vial containing sterile water diluent. Each RSVpreF vaccine contains 120 mcg of RSVpreF vaccine (60 mcg each of RSV A and RSV B antigens) and is reconstituted to 0.5 mL. After reconstitution, RSVpreF must be administered within 4 hours. The most common AEs associated with the RSVpreF vaccine in pregnant patients were injection site reactions, headache, muscle pain, and nausea.⁶ Table 2⁵ reviews several key counseling points for pharmacists.

CONCLUSION

Pharmacists play a crucial role in advocating for vaccination and prevention of disease. Through the approval of a maternal RSV vaccine, pharmacists can protect the youngest and most vulnerable patients.

References

1. RSV surveillance and research. CDC. Updated July 17, 2023. Accessed March 29, 2024. https://www.cdc.gov/rsv/research/index.html

2. Committee on Infectious Diseases, American Academy of Pediatrics. Respiratory syncytial virus. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021-2024 Report of the Committee on Infectious Diseases. 32nd ed. American Academy of Pediatrics; 2021:628-636.

3. Vaccines during and after pregnancy. CDC. Updated September 29, 2023. Accessed March 29, 2024. https://www.cdc.gov/vaccines/pregnancy/vaccduring-after.html

4. Yonts AB, Gaviria-Agudelo C, Kimberlin DW, O’Leary ST, Paulsen GC. Fall 2023 ACIP update on meningococcal, RSV, COVID-19, and other pediatric vaccines. Pediatrics. 2024;153(3):e2023064990. doi:10.1542/peds.2023-064990

5. Fleming-Dutra KE, Jones JM, Roper LE, et al. 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. Morb Mortal Wkly Rep. 2023;72(41):1115-1122. doi:10.15585/mmwr.mm7241e1

6. Abrysvo. Prescribing information. Pfizer; 2024. https://www.fda.gov/media/168889/download

7. Arexvy. Prescribing information. GlaxoSmithKline; 2023. https://www.fda.gov/media/167805/download

8. 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;388(16):1451-1464. doi:10.1056/NEJMoa2216480

9. Dieussaert I, Hyung Kim J, Luik S, et al. RSV prefusion F protein-based maternal vaccine - preterm birth and other outcomes. N Engl J Med. 2024;390(11):1009-1021. doi:10.1056/NEJMoa2305478

10. A study of mRNA-1345 vaccine targeting respiratory syncytial virus in pregnant women and in infants born to vaccinated mothers. ClinicalTrials.gov. Updated February 28, 2024. Accessed March 29, 2024. https://clinicaltrials.gov/study/NCT06143046

11. Moderna Receives US FDA Approval for RSV Vaccine mRESVIA(R). News release. Moderna. May 31, 2024. Accessed June 11, 2024. https://investors.modernatx.com/news/news-details/2024/Moderna-Receives-U.S.-FDA-Approval-for-RSV-Vaccine-mRESVIAR/default.aspx