Pediatrics
Maternal RSV vaccination and nirsevimab: safe alone or together
Clinical takeaway: For most infants, either maternal RSV vaccination during pregnancy or infant nirsevimab alone provides robust early protection against RSV. When both are given—intentionally or inadvertently—this interim analysis suggests the sequential approach is safe and well tolerated, supporting current AAP guidance for special circumstances.
Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract disease and hospitalization in young infants. Two preventive strategies are now available in the US: maternal RSV prefusion F vaccination (Abrysvo) during pregnancy and infant immunization with the long‑acting monoclonal antibody nirsevimab. Until now, these approaches had not been systematically studied together.
In a prospective, randomized, open‑label phase 4 trial conducted at eight U.S. sites, 181 mother–infant pairs were assigned to one of four strategies: maternal Abrysvo vaccine alone, maternal Abrysvo plus infant nirsevimab at birth, maternal Abrysvo plus infant nirsevimab at 3 months, or infant nirsevimab alone at birth. This interim analysis includes safety and immunogenicity data through four months of infant follow‑up.
Safety outcomes were reassuring across all groups. No vaccine‑ or product‑related serious adverse events occurred in mothers or infants. Among infants receiving nirsevimab, local reactions occurred in about 17% and systemic symptoms (most commonly sleepiness or irritability) in about 60%; all were mild to moderate and resolved within days.
Maternal vaccination led to a 17‑fold increase in maternal RSV neutralizing antibody titers at delivery, with efficient transplacental transfer (cord‑to‑maternal ratios >1.3), resulting in high antibody levels in newborns. Infants who received nirsevimab—either alone or after maternal vaccination—also achieved high RSV‑A and RSV‑B antibody titers, with only modest waning through three months. Across strategies, infant antibody levels were comparable to those seen in prior efficacy trials of Abrysvo and nirsevimab.
The study was not designed to compare clinical efficacy or RSV infection rates, but the findings support the immunologic complementarity and safety of these approaches. Most infants will not need both interventions; however, when dual exposure is indicated (e.g., birth soon after maternal vaccination, high‑risk infants, or uncertain maternal vaccination history), this interim analysis provides reassurance that combined use is safe and immunogenic.
In an accompanying commentary, Michael Rajnik, MD, and Martin Ottolini, MD, MEd, place the trial findings in historical context, noting that protecting young infants from RSV has been a multigenerational challenge marked by earlier setbacks and safety concerns. They emphasize that the availability of multiple effective strategies—maternal vaccination, infant monoclonal antibody prophylaxis, or selective use of both—represents a meaningful advance in RSV prevention. The authors underscore the importance of individualized, risk‑based decision‑making and note that the trial’s safety data provide reassurance when sequential exposure occurs in real‑world clinical scenarios.
Source: Rostad CA, et al. (2026, May 4). Pediatrics. Maternal RSV vaccination, infant nirsevimab, or both: interim analysis of a randomized trial