Nirsevimab Outperforms Maternal Vaccination in Reducing Severe RSV Outcomes: Insights from Comparative Real-World Evidence

High-Level Highlights

Two landmark studies published in late 2024 have provided the first comprehensive real-world comparison of the two primary strategies for preventing severe respiratory syncytial virus (RSV) in infants: maternal vaccination with RSVpreF and passive immunization with the long-acting monoclonal antibody nirsevimab. Key takeaways include:

• Nirsevimab was associated with a 26% lower risk of RSV-associated hospitalization compared to maternal RSVpreF vaccination in a large French cohort.
• In the United States, nirsevimab demonstrated 81% effectiveness against hospitalization, while maternal vaccination showed 70% effectiveness among infants under 6 months.
• Nirsevimab significantly reduced the risk of severe outcomes, including a 42% reduction in PICU admissions and a 43% reduction in the need for mechanical ventilation compared to maternal vaccination.
• Both strategies successfully reduced the population-level burden of RSV, with US hospitalization rates for infants under 1 year falling by nearly half compared to pre-implementation seasons.

The Evolving Landscape of RSV Prevention

Respiratory syncytial virus (RSV) remains a leading global cause of lower respiratory tract infections and the primary driver of infant hospitalizations in high-income countries. Until recently, prevention was limited to palivizumab, a monoclonal antibody reserved for high-risk infants. The landscape shifted dramatically with the approval of nirsevimab (Beyfortus), a long-acting monoclonal antibody, and the maternal RSVpreF vaccine (Abrysvo), designed to provide passive immunity via placental antibody transfer.

Clinicians and policy makers have faced a critical question: which strategy is more effective in a real-world setting? While clinical trials demonstrated high efficacy for both, head-to-head data were lacking until the 2024-2025 season. The studies by Moline et al. and Jabagi et al. provide the necessary evidence to refine clinical recommendations and public health strategies.

Study Design and Methodological Approaches

The US Surveillance Study (Moline et al.)

Conducted across seven pediatric medical centers in the United States, this population-based surveillance study utilized a test-negative case-control design. The researchers enrolled 5,029 children under 2 years of age with medically attended acute respiratory illness (ARI). The study estimated the effectiveness of maternal vaccination (administered at 32-36 weeks’ gestation) and nirsevimab (administered to newborns or infants under 8 months). The primary endpoints were medically attended RSV-associated ARI and hospitalization.

The French Comparative Cohort (Jabagi et al.)

This study utilized the French National Health Data System to perform a 1:1 matched cohort analysis. It included 42,560 infants, comparing those whose mothers received RSVpreF to those who received nirsevimab prior to hospital discharge. Unlike the US study, this was a direct comparative effectiveness study, focusing on hospitalization for RSV-associated lower respiratory tract infection and severe secondary outcomes like Pediatric Intensive Care Unit (PICU) admission and ventilator support.

Key Findings: Comparative Effectiveness and Impact

Superiority of Nirsevimab in Severe Disease Prevention

The French study (Jabagi et al.) provided the most direct evidence of nirsevimab’s clinical edge. Of the 481 hospitalizations observed, 44.1% occurred in the nirsevimab group versus 55.9% in the maternal vaccine group. After adjustment, nirsevimab was associated with a significantly lower risk of hospitalization (aHR 0.74; 95% CI, 0.61-0.88). Perhaps more critically, nirsevimab showed even greater relative benefits for the most severe cases:

• PICU Admission: 42% lower risk with nirsevimab (aHR 0.58).
• Ventilator Support: 43% lower risk with nirsevimab (aHR 0.57).
• Oxygen Therapy: 44% lower risk with nirsevimab (aHR 0.56).

Effectiveness in the US Context

The US data (Moline et al.) echoed these findings through the lens of vaccine effectiveness (VE). Among infants under 6 months, maternal vaccine effectiveness against hospitalization was 70% (95% CI, 37%-86%). In comparison, nirsevimab effectiveness against hospitalization for infants under 8 months was 81% (95% CI, 71%-87%). Notably, nirsevimab’s protection remained robust (77%) even 130 to 210 days after administration, suggesting that a single dose provides comprehensive coverage for the duration of a standard RSV season.

Population-Level Impact

Beyond individual protection, the US study quantified the broader public health impact. The introduction of these products led to a 41% to 51% reduction in RSV-associated hospitalizations among infants aged 0 to 11 months. The most dramatic impact was seen in the youngest cohort (0-2 months), where hospitalizations were reduced by up to 63% compared to historical data from 2017-2020.

Expert Commentary and Clinical Interpretation

The data suggest that while maternal vaccination is a highly effective tool, nirsevimab provides a more potent and direct form of protection. Several biological and logistical factors may explain this difference. Maternal vaccination relies on the efficient transfer of antibodies across the placenta, which can be influenced by the timing of vaccination relative to delivery and maternal immune health. In contrast, nirsevimab provides a standardized dose of high-affinity antibodies directly to the infant, bypassing the variability of placental transfer.

However, clinicians must consider the “real-world” implementation challenges. Maternal vaccination can be integrated into routine prenatal care, potentially reaching infants before they are even born. Nirsevimab requires administration to the infant, which depends on supply chain stability and healthcare access at the time of birth or early infancy. During the 2023-2024 season, nirsevimab faced significant supply shortages, a factor that makes maternal vaccination an essential secondary or primary option depending on local availability.

Limitations of these studies include their observational nature and the fact that they represent only the first full season of implementation. Long-term durability across multiple seasons and the potential for viral escape mutations in the RSV F protein remain areas for ongoing surveillance.

Summary and Clinical Takeaways

The 2024-2025 RSV season marks a turning point in pediatric medicine. The combination of maternal vaccination and nirsevimab has successfully halved the infant hospitalization rate for RSV in monitored regions. While nirsevimab appears to offer superior protection against severe outcomes and PICU admissions, both strategies are significantly better than no prophylaxis.

For clinicians, the choice between maternal vaccination and nirsevimab should be guided by infant risk factors, timing of the RSV season, and product availability. In scenarios where nirsevimab is available, it may be the preferred choice for maximizing protection against severe disease. However, the maternal vaccine remains a vital pillar of the RSV prevention strategy, ensuring that infants are born with a baseline of protective immunity.

References

1. Moline HL, Tannis A, Goldstein L, et al. Effectiveness and Impact of Maternal RSV Immunization and Nirsevimab on Medically Attended RSV in US Children. JAMA Pediatr. Published online December 22, 2024. doi:10.1001/jamapediatrics.2025.5778.
2. Jabagi MJ, Bertrand M, Gabet A, et al. Nirsevimab vs RSVpreF Vaccine for Respiratory Syncytial Virus-Related Hospitalization in Newborns. JAMA. Published online December 22, 2024. doi:10.1001/jama.2025.24082.