Real-World Effectiveness of Adjuvanted RSVPreF3 Vaccination in the Prevention of Respiratory Syncytial Virus-Related Hospitalization Among US Adults 60 Years of Age and Older

BACKGROUND: There is a growing body of evidence on the real-world effectiveness of adjuvanted respiratory syncytial virus (RSV) prefusion F3 (RSVPreF3) vaccination against RSV-related hospitalization among older adults. However, additional research is needed to further estimate vaccine effectiveness (VE) in subgroups at increased risk for severe RSV disease. RESEARCH QUESTION: What is the VE of adjuvanted RSVPreF3 vaccination against RSV-related hospitalization among adults aged ≥ 60 years in the United States, including subgroups at increased risk for severe RSV disease? STUDY DESIGN AND METHODS: This retrospective cohort study used claims data from the Optum Research Database. Adjuvanted RSVPreF3-vaccinated and unvaccinated adults aged ≥ 60 years were identified (August 2023-May 2024) and exact-matched 1:4 by age, sex, insurance type, and US state. Vaccination date was assigned as the index date. Baseline characteristics were measured during the 12-month preindex period, with continuous enrollment required, and were balanced using propensity score-based weighting. Participants were monitored from 14 days postindex to the earliest of: disenrollment, death, RSV vaccination, or end of the analysis period (May 31, 2024). Hazard ratios (HRs) were estimated by Cox proportional hazards regression, comparing risk of RSV-related hospitalization, with VE calculated as (1 - HR) × 100%. RESULTS: The study included 520,440 vaccinated and 2,081,760 unvaccinated participants. Median follow-up was 5.6 months, with a maximum of 9.7 months. Estimated VE was 75.6% (95% CI, 69.8%-80.2%). VE estimates in key subgroups included 72.5% (64.3%-78.8%) among those with chronic pulmonary disease, 72.2% (64.1%-78.4%) among those with cardiovascular disease, 82.3% (74.2%-87.9%) among those with diabetes, and 71.4% (57.0%-81.1%) among those who were immunocompromised. INTERPRETATION: These findings highlight the effectiveness of adjuvanted RSVPreF3 vaccination in preventing RSV-related hospitalization among older adults, including those at increased risk, suggesting that vaccination is an effective strategy in reducing RSV disease burden.