AHFS Class:

• Vaccines 80:12

Generic Name(s):

• Respiratory Syncytial Virus Vaccine

• Recombinant Stabilized RSV A Prefusion F Antigen

• Recombinant Stabilized RSV B Prefusion F Antigen

Respiratory syncytial virus (RSV) vaccine is a bivalent RSV stablized prefusion F protein-based (RSV preF) vaccine that stimulates active and passive immunity to RSV infection; the antigen component contains recombinant RSV preF A and RSV preF B proteins.1

Prevention of Lower Respiratory Tract Disease Caused by Respiratory Syncytial Virus (RSV)

Immunization of Pregnant Individuals

RSV preF vaccine is used for active immunization of pregnant individuals at 32 through 36 weeks gestational age for the prevention of lower respiratory tract disease (LRTD) and severe LRTD caused by RSV in infants from birth through 6 months of age.1

Efficacy of RSV preF vaccine for this indication was established in a randomized, double-blind, placebo-controlled, phase 3 study that assessed the effects of the vaccine in preventing RSV-associated LRTD in infants born to individuals vaccinated during pregnancy.1,2 Pregnant women ≤49 years of age at 24 through 36 weeks' gestation were enrolled at various study sites in the northern and southern hemispheres and randomized to receive a single IM injection of the vaccine or placebo.1,2 The primary efficacy end points were RSV-associated severe LRTD and RSV-associated LRTD in infants within 90, 120, 150, and 180 days of birth.1,2 RSV-associated LRTD was defined as a confirmed RSV illness with one or more of the following respiratory symptoms: tachypnea (respiratory rate ≥60 breaths/minute [<2 months of age], ≥50 breaths/minute [≥2 to 12 months of age], or ≥40 breaths/minute [≥12-24 months of age]); SpO₂ measured in room air <95%; and/or chest wall indrawing.1 RSV-associated severe LRTD was a subset defined as meeting the RSV LRTD criteria plus at least one of the following: tachypnea (respiratory rate ≥70 breaths/minute [<2 months of age], ≥60 breaths/minute [≥2 to 12 months of age], or ≥50 breaths/minute [≥12 to 24 months of age]); SpO₂ measured in room air <93%; high-flow nasal cannula or mechanical ventilation (invasive or noninvasive), intensive care unit (ICU) admission for >4 hours, and/or failure to respond/unconscious.1

RSV preF vaccine met the success criterion for vaccine efficacy with respect to reducing severe RSV-associated LRTD in infants at all timepoints evaluated (vaccine efficacy of 81.8% at 90 days, 73.9% at 120 days, 70.9% at 150 days, and 69.4% at 180 days).1,2 Results did not meet statistical criterion for sucess for the other end point in reducing LRTD due to RSV; however, the vaccine had a clinically meaningful effect after 90 days through 180 days after birth by reducing the incidence of hospitalization for RSV-associated LRTD.1,2

Clinical Perspective

RSV causes respiratory tract infections in individuals of all age groups and is a common cause of LRTD in infants.21 RSV is the leading cause of hospitalization among US infants.21

Vaccination of pregnant persons with a single dose of RSV preF vaccine (Abrysvo^®) at 32 to 36 weeks' gestation has demonstrated efficacy in preventing RSV-associated LRTD in infants <6 months of age.21 The US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommends seasonal administration of maternal RSVpreF vaccine (i.e., during September through end of January in most of the continental US) in pregnant persons as a one-time dose at 32-36 weeks' gestation for prevention of RSV-associated LRTD in infants <6 months of age.21 Alternatively, nirsevimab may be given to the infant, but both therapies are not needed for most infants.21 ACIP states that all infants should be protected against RSV-associated LRTD through the use of one of these products.21

Administering maternal RSV preF vaccine starting in September (1-2 months before the anticipated start of the RSV season) and continuing through January (2-3 months before the anticipated end of the RSV season) maximizes cost-effectiveness and benefits of the vaccine in the continental US.21 Areas with different seasonality should follow regional guidance on the timing of maternal RSVpreF vaccination.21

Immunization of Older Adults

RSV preF vaccine is used for active immunization for the prevention of LRTD caused by RSV in individuals 60 years of age and older.1

Efficacy of RSV preF vaccine in adults ≥60 years of age is based principally on an ongoing, muticenter, randomized, double-blind, placebo-controlled, phase 3 study.1,6 Individuals with stable chronic medical conditions including cardiopulmonary disease were allowed to participate; however, immunocompromised patients other than those with stable human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus infection were excluded.1,6 Participants were randomized to receive a single IM injection of the vaccine or placebo.1,6 Following vaccination, participants were monitored for the onset of acute respiratory illness symptoms (i.e., new or increased sore throat, nasal congestion, nasal discharge, cough, wheezing, sputum production, or shortness of breath) and tested for RSV if any symptoms developed.1,6 RSV-associated LRTD was defined as confirmed RSV illness with ≥2 of the following respiratory symptoms within 7 days of symptom onset and lasting more than 1 day during the same illness: new or increased cough, wheezing, sputum production, shortness of breath, or tachypnea (≥25 breaths/min or 15% increase from resting baseline).1,6 RSV-associated severe LRTD was defined as meeting the RSV-LRTD criteria plus at least one of the following: hospitalization due to RSV-LRTD, new or increased oxygen supplementation, or mechanical ventilation including continuous positive airway pressure (CPAP).1,6,20 The median duration of follow-up for efficacy was 7 months.1

Based on the interim analysis, vaccine efficacy for preventing a first episode of RSV-associated LRTD with at least 2 signs or symptoms was 66.7%, and vaccine efficacy for preventing a first episode of RSV-associated LRTD with at least 3 signs or symptoms (indicating a worse clinical disease presentation) was 85.7%.1,6

Clinical Perspective

RSV causes respiratory tract infections in individuals of all age groups.3,4 In older adults, RSV is a common cause of LRTD that can lead to severe disease requiring hospitalization for respiratory support, including supplemental oxygen and/or mechanical ventilation.4 Infection rates, ICU stays, and mortality are similar among older adults hospitalized with respiratory viral infections caused by RSV and influenza.3 Severity of RSV disease increases with age and comorbidities (e.g., chronic obstructive pulmonary disease, congestive heart failure, asthma).3

The US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommends that all adults ≥75 years of age receive a single dose of RSV vaccine.8 ACIP also recommends that adults 60-74 years of age who are at increased risk of severe RSV disease receive a single dose of RSV vaccine.8 Clinical considerations that place these adults at increased risk of severe RSV include lung disease, cardiovascular disease, moderate or severe immune compromise, diabetes mellitus with end-organ damage, severe obesity (BMI ≥40 kg/m²), neurologic or neuromuscular conditions, advanced chronic kidney disease, liver disorders, hematologic disorders, frailty, and other chronic medical conditions that a healthcare provider determines increases risk of severe disease due to respiratory infection.9 Residence in a nursing home or other long-term care facility may also increase the risk of severe RSV disease.9 Adults 60-74 years of age who are not at increased risk of severe RSV disease are not recommended to receive RSV vaccination based on ACIP guidelines.8,9

Although RSV vaccines are generally well-tolerated, a few cases of inflammatory neurologic events have been reported in clinical trials.20

General

Dispensing and Administration Precautions

• Appropriate medications and supplies for managing allergic reactions must be immediately available in the event that an acute anaphylactic reaction occurs following vaccine administration.1
• Syncope may occur following administration of injectable vaccines.1 Procedures should be in place to avoid injury from fainting; if syncope develops, patients should be observed until the symptoms resolve.5

Administration

IM Administration

Respiratory syncytial virus (RSV) preF vaccine solution for injection is administered only by IM injection.1 IM injections should preferably be made into the deltoid muscle.5

RSV preF vaccine solution for injection is available in 2 presentations.1 In one presentation, the vaccine is supplied in a kit that includes a vial of lyophilized antigen component (asterile white powder), a prefilled syringe containing sterile water diluent component, and a vial adapter.1 In the other presentation, the vaccine is supplied in cartons that include a vial of lyophilized antigen component and a vial containing the sterile water diluent component.1 For both presentations, reconstitute the lyophilized antigen component with the accompanying sterile water diluent as described in the manufacturer's prescribing information.1 After the vaccine is reconstituted, a single dose is either approximately 0.5 mL (for the vial and prefilled syringe presentation) or 0.5 mL (for the vial and vial presentation).1 Visually inspect the solution; the vaccine should be clear and colorless.1 Discard if discoloration or particulate matter is observed.1

After the vaccine is reconstituted, administer immediately or store at room temperature (15-30°C) and use within 4 hours; discard the vaccine if not used within 4 hours.1

Dosage

Prevention of Lower Respiratory Tract Disease Caused by RSV

Immunization in Pregnant Individuals at 32 through 36 Weeks Gestational Age

The dosage of RSV preF vaccine for active immunization in pregnant individuals at 32 through 36 weeks gestational age for the prevention of lower respiratory tract disease (LRTD) caused by RSV in infants from birth through 6 months of age is 0.5 mL administered as a single IM dose.1

The manufacturer states that safety and effectiveness of the vaccine in infants born to individuals vaccinated at <10 years of age not established.1

Immunization in Individuals 60 Years of Age

The dosage of RSV preF vaccine for active immunization for the prevention of LRTD caused by RSV in adults ≥60 years of age is 0.5 mL administered as a single IM dose.1

Contraindications

• History of severe allergic reaction (e.g., anaphylaxis) to any component of respiratory syncytial virus (RSV) vaccine.1

Warnings/Precautions

Potential Risk of Preterm Birth

A numerical imbalance in preterm births was observed in recipients of RSV preF vaccine compared to placebo recipients in 2 clinical studies.1 Available data are insufficient to establish or exclude a causal relationship to the drug.1

To avoid the potential risk of preterm birth before 32 weeks of gestation, administer RSV preF vaccine as indicated in pregnant individuals at 32 through 36 weeks gestational age.1 Pregnant individuals who were at increased risk of preterm birth were generally excluded from clinical studies of the vaccine.1

Preventing and Managing Allergic Vaccine Reactions

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the RSV preF vaccine.1

Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines, including the RSV preF vaccine.1 Procedures should be in place to prevent injury from fainting.1

Altered Immunocompetence

Immunocompromised persons, including those receiving immunosuppressive therapy, may have a diminished immune response to the RSV preF vaccine.1

Limitations of Vaccine Effectiveness

Vaccination with the RSV preF vaccine may not protect all recipients.1

Specific Populations

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to RSV preF vaccine during pregnancy.1 Individuals who receive the vaccine during pregnancy are encouraged to contact, or have their healthcare provider contact 1-800-616-3791 to enroll in or obtain information about the registry.1

In a randomized controlled trial that enrolled pregnant individuals, preterm births were higher in those who received RSV preF vaccine at 24 through 36 weeks' gestation compared to those who received placebo; however, available data are insufficient to establish or exclude a causal relationship to the drug.1 There was no evidence of a vaccine-associated increase in the risk of congenital anomalies or fetal deaths.1 To avoid the potential risk of preterm birth with use of RSV preF vaccine before 32 weeks of gestation, administer the vaccine as indicated in pregnant individuals at 32 through 36 weeks gestational age.1 RSV preF vaccine has not been studied in pregnant individuals <24 weeks gestational age, and those at increased risk for preterm birth.1

Results of a developmental toxicity study in animals showed no evidence of fetal harm or adverse effects on postnatal survival, growth, or development.1

Lactation

It is not known whether RSV preF vaccine is excreted in human milk.1 Data are not available to assess the effects of the vaccine on the breastfed infant or on milk production.1 The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for the RSV preF vaccine and any potential adverse effects on the breastfed child from the vaccine or from the underlying maternal condition.1 For preventative vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.1

Pediatric Use

The safety and effectiveness of RSV preF vaccine for prevention of RSV LRTD and severe RSV LRTD in infants born to individuals vaccinated at <10 years of age have not been established.1

The safety and effectiveness of RSV vaccine to prevent RSV LRTD in non-pregnant individuals <18 years of age via active immunization have not been established.1

Geriatric Use

RSV preF vaccine is approved for use in individuals ≥60 years of age.1 In the principal efficacy study, 62% of the participants were 60-69 years of age, 32% were 70-79 years of age, and 6% were ≥80 years of age.1

Common Adverse Effects

The most common local and systemic adverse reactions in pregnant individuals (≥10%) were pain at the injection site, headache, muscle pain, and nausea.1

The most common local and systemic adverse reactions in individuals ≥60 years of age (≥10%) were fatigue, headache, pain at the injection site, and muscle pain.1

Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed

No safety concerns were identifed when non-pregnant women received the RSV preF vaccine and Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, adsorbed) concomitantly.1,7 Immune responses to RSV A, RSV B, diphtheria, and tetanus were non-inferior to those after separate administration; however, geometric mean antibody concentrations (GMCs) to the acellular pertussis antigens were lower when the RSV vaccine was administered concomitantly with Tdap compared to when Tdap was administered alone.1,7

Concomitant administration of Tdap with the RSV vaccine in pregnant individuals has not been studied.1

Description

Respiratory syncytial virus (RSV) preF vaccine is a bivalent RSV stablized prefusion F protein-based (RSV preF) vaccine that stimulates active and passive immunity to RSV infection; the antigen component contains recombinant RSV preF A and RSV preF B proteins.1 RSV preF vaccine induces an immune response against RSV preF that protects against lower respiratory tract disease (LRTD) caused by RSV.1 The vaccine also induces passive immunization when antibodies to RSV antigens from individuals vaccinated in pregnancy are transferred transplacentally to protect infants <6 months of age against LRTD and severe LRTD caused by RSV.1 RSV F glycoprotein (prefusion and postfusion) mediates viral fusion and host-cell entry, elicits neutralizing antibodies, and is highly conserved across the 2 RSV subtypes (A and B).4

Advice to Patients

• Advise vaccine recipients of the potential benefits and risks of vaccination with the respiratory syncytial virus (RSV) preF vaccine.1
• Advise vaccine recipients to report any adverse events to their healthcare provideror to the Vaccine Adverse Event Reporting System at 1-800-822-7967 or [Web].1
• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1
• Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.1
• Inform patients of other important precautionary information.1

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Only references cited for selected revisions after 1984 are available electronically.

1. Pfizer Laboratories. Abrysvo^®(Respiratory Syncytial Virus Vaccine) prescribing information. NY, NY; 2024 Mar. [Web]

2. 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 20;388(16):1451-1464. . Epub 2023 Apr 5. [PubMed 37018474]

3. Kodama F, Nace DA, Jump RLP. Respiratory Syncytial Virus and Other Noninfluenza Respiratory Viruses in Older Adults. Infect Dis Clin North Am. 2017 Dec;31(4):767-790. [PubMed 29079159]

4. US Food and Drug Administration. Center for Biologics Evaluation and Research. Submission tracking number (STN): 125769/0: BLA Clinical review memorandum. From FDA website. [Web]

5. Kroger A, Bahta L, Hunter P. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP). Accessed on 2023 Jun 26. [Web]

6. Walsh EE, Pérez Marc G, Zareba AM et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med. 2023 Apr 20;388(16):1465-1477. Epub 2023 Apr 5. [PubMed 37018468.]

7. Peterson JT, Zareba AM, Fitz-Patrick D et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When Coadministered With a Tetanus, Diphtheria, and Acellular Pertussis Vaccine. J Infect Dis. 2022 Jun 15;225(12):2077-2086. [PubMed 34637519]

8. Center for Disease Control and Prevention. ACIP Recommendation. June 26-28, 2024.

9. Center for Disease Control and Prevention. ACIP Adult RSV Work Group Clinical Considerations: Respiratory Syncytial Virus (RSV) in Adults 60 and older. 2024 June 26.

20. Melgar M, Britton A, Roper LE, et al. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023. MMWR Morb Mortal Wkly Rep 2023;72:793-801.

21. 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. MMWR. 2023; 72:1115-22.