Nirsevimab cuts infant RSV hospitalization

RSV has been the leading cause of infant hospitalization in the United States for decades, accounting for roughly 58,000 to 80,000 hospitalizations annually in children under 5 before the arrival of effective preventive agents. Palivizumab, a monthly monoclonal antibody approved in 1998, reduced that burden in premature infants and those with specific comorbidities, but its short half-life and high cost made universal prophylaxis impractical. Full-term, otherwise healthy infants had no preventive option beyond supportive care and hand hygiene.

Nirsevimab was designed to address that gap. It targets a prefusion-stabilized epitope on the RSV fusion protein with higher potency and a longer half-life than palivizumab, enabling a single intramuscular dose at or near birth to provide protection for an entire RSV season. The phase 3 MELODY trial, led by Laura Hammitt of Johns Hopkins University, enrolled healthy late-preterm and term infants and demonstrated 76.4% efficacy against medically attended RSV lower respiratory tract infection, with a similar 76.8% efficacy against hospitalization specifically. ACIP recommended nirsevimab for all infants under 8 months entering their first RSV season in August 2023.

The 2023-24 season provided the first nationwide effectiveness data. CDC surveillance, published in MMWR in 2024, showed 90% effectiveness against RSV hospitalization in infants under 8 months, consistent with the trial estimates. That figure emerged from real-world use, which included variation in injection timing, storage, and the concurrent presence of other respiratory pathogens.

Hospitalization rates fell visibly in regions with high nirsevimab uptake, and the effect was measurable even against the background of maternal RSV vaccination, which had launched in the same season using a different mechanism: maternal immunization with Pfizer's Abrysvo during pregnancy to transfer passive antibody to the newborn via the placenta. The two approaches offered overlapping but not identical protection windows.

For pediatricians and neonatologists, the data confirmed that passive immunoprophylaxis for RSV now extends beyond the original high-risk palivizumab population to all newborns. Supply constraints during the first season limited uptake in some regions, which became a logistics problem distinct from the question of efficacy. The combination of maternal vaccine and infant antibody represented a two-product prevention model that had not previously existed for any common respiratory pathogen in the neonatal period.