At what age should Respiratory Syncytial Virus (RSV) vaccination be initiated in high-risk infants?

RSV Immunoprophylaxis for Children

All infants younger than 8 months born during or entering their first RSV season should receive nirsevimab (a single-dose long-acting monoclonal antibody), administered from October through March in most of the continental United States. 1

Current Standard of Care: Nirsevimab (2023 Guidelines)

The Advisory Committee on Immunization Practices (ACIP) issued updated recommendations in August 2023 that fundamentally changed RSV prevention, replacing the older palivizumab approach for most infants with the more convenient single-dose nirsevimab. 1

First RSV Season (All Infants)

• Infants <8 months of age born during or entering their first RSV season should receive a single intramuscular dose of nirsevimab 1
• Dosing by weight: 50 mg if <5 kg body weight; 100 mg if ≥5 kg body weight 2
• Timing: Administer from October through end of March in most of the continental United States, ideally within 1 week of birth for infants born during RSV season 1
• Infants born shortly before RSV season: Give nirsevimab within 1 week of birth, either during birth hospitalization or in outpatient setting 1
• Premature infants with prolonged hospitalizations: Administer shortly before or promptly after hospital discharge 1
• Use chronologic age (not corrected age) to determine timing and eligibility 1

This represents a major advance over palivizumab, which required 5 monthly injections. Nirsevimab provides protection with a single dose throughout the RSV season. 1

Second RSV Season (High-Risk Children Only)

• Children aged 8-19 months at increased risk for severe RSV disease entering their second RSV season should receive nirsevimab 1
• Dosing: 200 mg as a single intramuscular dose 2

High-risk conditions for second season include: 1

• Chronic lung disease of prematurity requiring medical therapy within 6 months before RSV season
• Hemodynamically significant congenital heart disease (cyanotic or acyanotic with congestive heart failure requiring medication, moderate-to-severe pulmonary hypertension)
• Severe immunocompromise during RSV season
• Cystic fibrosis with manifestations of severe lung disease or weight-for-length <10th percentile
• Anatomic pulmonary abnormalities or neuromuscular disorders impairing airway clearance
• American Indian/Alaska Native children (due to 4-10 times higher hospitalization rates) 1

Geographic Considerations

• Most continental U.S.: October through March administration 1
• Southern U.S.: Earlier onset typical; may begin in September 1
• Alaska: Less predictable seasonality with longer duration; consult local guidance 1
• Tropical climates (southern Florida, Hawaii, Puerto Rico, Guam, Pacific Islands, Virgin Islands): Unpredictable seasonality; consult territorial guidance 1

Coadministration with Vaccines

• Nirsevimab can be given simultaneously with routine childhood vaccines at the same visit 1
• No interference with immune response to other immunizations expected 1

Clinical Impact

Recent 2024-25 season data demonstrate nirsevimab's real-world effectiveness, with 43-52% reduction in RSV hospitalizations among infants aged 0-7 months compared to pre-nirsevimab seasons, with the largest reductions (52%) in infants 0-2 months of age. 3

Legacy Approach: Palivizumab (Pre-2023)

While nirsevimab has replaced palivizumab for most infants, understanding the older palivizumab guidelines remains relevant for interpreting historical literature and for rare situations where nirsevimab is unavailable. 1

Palivizumab Dosing (Historical)

• 15 mg/kg intramuscularly monthly throughout RSV season 1
• Maximum 5 doses per season 1
• Additional dose required after cardiac bypass surgery or ECMO (58% decrease in serum concentration post-procedure) 1

Palivizumab Eligibility Criteria (Historical)

The 2009-2014 AAP guidelines restricted palivizumab to specific high-risk groups: 1

Infants ≤28 weeks 6 days gestation:

• Up to 12 months of age at start of RSV season 1
• Maximum 5 doses 1

Infants 29-31 weeks 6 days gestation:

• Up to 6 months of age at start of RSV season 1
• Maximum 5 doses 1

Infants 32-34 weeks 6 days gestation:

• Only if ≥2 risk factors present and <6 months at season start 1
• Risk factors: childcare attendance, school-aged siblings, environmental air pollutants, congenital airway abnormalities, severe neuromuscular disease 1
• Up to 90 days of age (3 months) at season start 1

Important note: The 2014 AAP policy change that restricted palivizumab for 29-34 week infants was followed by a 2.09-fold increase in RSV hospitalizations in this population, demonstrating the consequences of limiting prophylaxis. 4 This evidence supported the broader ACIP recommendation for universal nirsevimab coverage in 2023.

Maternal RSV Vaccination Alternative

Pregnant individuals can receive RSVPreF3 vaccine between 32 0/7 and 36 6/7 weeks gestation to protect their infant during the first 6 months of life. 5

Key Decision Point

• Either maternal vaccination OR infant nirsevimab is recommended—not both for most infants 5
• If mother received RSV vaccine during pregnancy (32-36 weeks), infant typically does not need nirsevimab 5
• If mother did not receive RSV vaccine, infant should receive nirsevimab 5
• Product availability may influence this decision during implementation 5

Critical Pitfalls to Avoid

• Never use palivizumab or nirsevimab to treat established RSV infection—these are prophylactic products only, with no therapeutic benefit once infection occurs 6, 7
• Do not delay nirsevimab for infants born during RSV season—administer within first week of life, ideally during birth hospitalization 1
• Do not use corrected age for premature infants when determining nirsevimab eligibility—always use chronologic age 1
• Do not give both maternal vaccine and infant nirsevimab routinely—one or the other provides adequate protection for most infants 5
• Do not restrict nirsevimab to high-risk infants only—79% of RSV hospitalizations occur in previously healthy term infants without underlying conditions 1

Contraindications

• Severe allergic reaction (anaphylaxis) to previous dose or product component 1
• Follow ACIP general best practices for bleeding disorders when administering intramuscular injections 1