Maternal Respiratory Syncytial Virus Prefusion F Vaccination and Acute Respiratory Illness in Infants

Importance: The bivalent respiratory syncytial virus prefusion F (RSVpreF) vaccine was licensed in the US in September 2023 to prevent RSV-associated lower respiratory tract disease (LRTD) in infants via maternal immunization. Clinical data on vaccine effectiveness are limited. Objective: To estimate the effectiveness of maternal RSVpreF vaccination against hospitalization for RSV-associated acute respiratory illness (ARI) and LRTD among infants 90 days or younger during the first 2 postlicensure RSV seasons. Design, Setting, and Participants: This retrospective case-control study (Effectiveness of ABRYSVO Maternal Respiratory Syncytial Virus Vaccine Against RSV in Infants in Western Pennsylvania study) using a test-negative design was conducted within a single health system in western Pennsylvania during the 2023-2024 and 2024-2025 RSV seasons. The analysis included infants 90 days or younger born between October 1, 2023, and April 15, 2024, or between September 1, 2024, and April 30, 2025, who were hospitalized with ARI and tested for RSV using nucleic acid amplification or rapid antigen testing. Exposure: Maternal RSVpreF vaccination administered at gestational age between 32 weeks 0 to 7 days and 36 weeks 6 to 7 days and at least 14 days before delivery. Main Outcomes and Measures: The primary outcome was RSV-associated ARI requiring hospitalization. The secondary outcome was RSV-associated LRTD requiring hospitalization. Vaccine effectiveness was estimated as (1 - Adjusted Odds Ratio) × 100% comparing the odds of maternal RSVpreF vaccination among RSV-positive infants (cases) vs RSV-negative infants (controls) using multivariable logistic regression. Results: Among 274 included infants (83 with RSV and 191 controls), the mean (SD) age at admission was 29.5 (21.1) days; 143 infants (52.2%) were male. Among these, 11 of 83 infants with RSV (13.3%) and 71 of 191 controls (37.2%) were born to RSVpreF-vaccinated individuals. Vaccine effectiveness was estimated to be 67.6% (95% CI, 33.2%-85.4%) against RSV-associated ARI hospitalization and 69.0% (95% CI, 25.5%-88.0%) against RSV-associated LRTD hospitalization from 0 through 90 days of age. Among infants aged 0 to 30 days, vaccine effectiveness against RSV-associated ARI hospitalization was estimated to be 74.2% (95% CI, 25.4%-93.0%). Conclusions and Relevance: Maternal RSVpreF vaccination was associated with protection against RSV-associated ARI and LRTD hospitalization among infants 90 days or younger. These findings provide early clinical evidence supporting the effectiveness of maternal RSVpreF vaccination in preventing RSV-associated hospitalization in infants.