Understanding AAP's New RSV Immunization Guidelines for Infants

Respiratory syncytial virus (RSV) remains a leading cause of hospitalization among infants, particularly those under 1 year of age. RSV's ability to overwhelm young immune systems necessitates effective passive immunoprophylaxis strategies to safeguard infant health. In response, the American Academy of Pediatrics (AAP) has issued updated guidance on RSV, clarifying how clinicians should protect infants during their first RSV season.

Monoclonal antibodies like nirsevimab and palivizumab are central to RSV prevention strategies; both target the RSV fusion protein to block the virus from infecting host cells. Current guidance specifies that most infants entering their first RSV season should receive a single dose of nirsevimab, while palivizumab is reserved for select high‑risk groups, such as infants with significant prematurity or chronic lung disease of prematurity, and some infants with hemodynamically significant heart disease.

Scheduling monoclonal antibody prophylaxis according to RSV seasonality is crucial for optimal protection of infants. Timing is key: a single dose of nirsevimab generally provides season‑long protection, whereas palivizumab requires monthly dosing during the RSV season for eligible high‑risk infants. This contrast can simplify care for most families while ensuring ongoing protection for those with elevated risk.

Coordination with maternal vaccination is also important: CDC/ACIP recommend the RSVpreF vaccine during 32–36 weeks’ gestation, and when given at least 14 days before birth, most infants will not require nirsevimab unless specific risk factors are present. This alignment helps avoid redundant prophylaxis while maintaining adequate protection for newborns.

Evidence from large trials supports preventative measures: in MELODY, nirsevimab significantly reduced medically attended RSV lower respiratory tract infection (LRTI) in healthy term and late‑preterm infants, with favorable safety; similar benefits were observed in the pragmatic HARMONIE study for outcomes including hospitalization. For example, in the HARMONIE study, nirsevimab was associated with a substantial reduction in RSV‑related hospitalizations in infants during their first season, with adverse events similar to control groups in frequency and severity. Nirsevimab has demonstrated favorable safety and efficacy in large trials, while palivizumab remains an option for high‑risk infants.

Aligning clinics to administer nirsevimab at the start of the local RSV season can streamline workflows and reduce missed opportunities. For infants who qualify for palivizumab, establishing reliable monthly follow‑up supports continuous protection throughout the season.

From a practice and policy standpoint, the combination of season‑long protection from a single nirsevimab dose, targeted use of monthly palivizumab for high‑risk infants, and trial‑demonstrated reductions in medically attended RSV disease and hospitalizations offers tangible benefits for families and health systems. Taken together, these recommendations represent a significant advancement, supported by quantified reductions in RSV disease and clear guidance on who should receive which product and when.

Key Takeaways

• AAP’s guidance recommends nirsevimab for most infants entering their first RSV season to reduce RSV‑LRTI and hospitalizations, while palivizumab remains for select high‑risk infants.
• Scheduling prophylaxis with RSV seasonality is key: nirsevimab is a single dose for most infants; palivizumab requires monthly dosing for eligible high‑risk infants.
• Maternal RSVpreF vaccination at 32–36 weeks’ gestation can obviate the need for infant nirsevimab when administered at least 14 days before birth, with exceptions for specific risk scenarios.