Takeaways
- Nirsevimab provided the greatest overall reduction in RSV-LRTD burden, preventing more hospitalizations, emergency visits, and primary care encounters than clesrovimab or RSVpreF maternal vaccination.
- Modeled cost-effectiveness consistently favored nirsevimab, with the lowest cost per RSV-LRTD and hospitalization averted and the smallest number needed to immunize across strategies.
- Maternal RSVpreF vaccination offered more modest impact, particularly for preterm infants due to limited antibody transfer, reinforcing the need for direct infant immunization to ensure comprehensive population protection.
A newly published US modeling study reports that respiratory syncytial virus (RSV) continues to generate substantial disease burden among infants, even under the historical standard of practice in which only high-risk infants received palivizumab. The model estimated 523,594 medically attended RSV-LRTD events and 44,483 hospitalizations each year in infants younger than 12 months.1,2
Researchers noted that the majority of medically attended illnesses occurred in healthy late-preterm and term infants, stating that “the burden was largest amongst healthy infants born late preterm or term.” Infants born outside the typical October–March RSV season accounted for 42% of hospitalizations, reaffirming the need for year-round infant protection.
How does nirsevimab perform compared with other RSV prevention options?
According to the analysis, nirsevimab—an extended half-life monoclonal antibody administered directly to infants—demonstrated the greatest projected reduction in RSV-LRTD outcomes across the full US birth cohort.
Modeling estimated that nirsevimab would avert 364,204 RSV-LRTD cases, including 32,404 hospitalizations, 88,647 emergency department visits, and 243,103 primary care visits. Investigators reported that nirsevimab use “would have averted an estimated $1,289 million in direct and indirect costs.”
Clesrovimab, another monoclonal antibody with a shorter half-life, showed variable impact depending on the assumed duration of protection. Across 100-day, 120-day, and 150-day protection scenarios, clesrovimab was estimated to prevent 173,276 to 261,358 RSV-LRTD events and 23,957 to 30,483 hospitalizations. The study highlighted uncertainty surrounding clesrovimab’s durability, noting “important questions about sustained protection throughout the 150-day RSV season.”
What is the impact of RSVpreF maternal vaccination on infant outcomes?
The study also evaluated outcomes associated with RSVpreF maternal vaccination, administered at 32 to 36 weeks of gestation. When coverage was modeled at levels equivalent to monoclonal antibody strategies, seasonal maternal vaccination prevented 76,915 RSV-LRTD events and 9,649 hospitalizations, corresponding to an estimated $345 million in savings.
However, protection varied substantially by gestational age. Due to reduced antibody transfer in early preterm births, only 13.4% of infants born preterm were projected to receive adequate protection, compared with 85.8% of late-preterm and term infants. Authors reported that this could “result either in a lack of protection in the most vulnerable…or in additional expenses by administering nirsevimab to ensure protection.”
How do cost-effectiveness and number needed to immunize compare across strategies?
Efficiency measures also favored nirsevimab. The number needed to immunize (NNI) to prevent one RSV-LRTD event was lowest for nirsevimab (9 infants). Clesrovimab required 12–17 infants, depending on modeled protection duration, while seasonal maternal vaccination required 19 maternal vaccinations to prevent one event.
Cost-effectiveness findings were similar. Nirsevimab had the lowest estimated cost per RSV-LRTD averted ($8), compared with $545–$2,195 for clesrovimab and $1,242 for seasonal maternal vaccination. For hospitalizations, nirsevimab’s cost was projected at $89 per case avoided, compared with $4,670–$15,875 for clesrovimab.
What do these findings mean for infant RSV prevention programs?
Across all modeled scenarios, nirsevimab provided the greatest projected clinical and economic benefit for infants entering their first RSV season. Investigators concluded that “all-infant protection with nirsevimab was estimated to avert more events for all infant subgroups compared to clesrovimab or RSVpreF maternal vaccination,” with the greatest advantage observed in infants born before the start of the RSV season.
The authors highlighted that sustained protection throughout the full 5- to 6-month RSV season is a key determinant of impact, noting that nirsevimab’s longer half-life may provide more consistent coverage across infant subgroups.
References
- Kieffer A, Hodges E, Greenberg M, Neary MP. Comparison of the public health impact of RSV disease prevention options for infants: a static decision model of the US birth cohort. Expert Review of Vaccines. 2025;24(1):1086-1098. doi:https://doi.org/10.1080/14760584.2025.2591816
- Hamid S, Winn A, Parikh R, et al. Seasonality of respiratory syncytial virus - United States, 2017–2023. MMWR Morb Mortal Wkly Rep. 2023;72(14):355–361.
