RSV Bivalent Prefusion F Protein Vaccine in Pregnancy and Protection Against RSV-Associated Illness in Infants

Abstract

Importance The respiratory syncytial virus (RSV) bivalent prefusion F protein vaccine (RSVpreF) administered during pregnancy has demonstrated efficacy in protecting infants against early-life RSV disease in the pivotal clinical trial. Objective To conduct a systematic review and meta-analysis to synthesize real-world evidence on the effectiveness of RSVpreF in preventing RSV-associated lower respiratory tract infection (LRTI) in infants. Data Sources PubMed, Scopus, and Europe PMC were searched from January 1, 2020, through January 30, 2026. Study Selection A total of 1144 studies were initially identified. Eligible were nonrandomized studies reporting the effectiveness of RSVpreF vaccine in pregnancy in the prevention of RSV-associated LRTI in infants. Data Extraction and Synthesis All studies were screened independently by 2 reviewers. Data were extracted on RSV-associated outcomes among infants born to women who received RSVpreF vaccination during pregnancy and infants born to unvaccinated women. Main Outcomes and Measures The primary outcome was RSV-associated LRTI hospitalization. Odds ratios (ORs) were pooled using random-effects meta-analysis with the Hartung-Knapp adjustment and Sidik-Jonkman estimator. Vaccine effectiveness against RSV-associated LRTI hospitalization was calculated as (1 − OR) × 100% and assessed in infants from birth to age 3 months and from birth to 6 months, separately. The limited available data precluded meta-analysis of effectiveness against the secondary outcomes of RSV-associated emergency department visits, intensive care unit admissions, and death. Results A total of 7 studies were included, comprising 7112 infants, of whom 2684 were born to vaccinated mothers. The studies collected data from January 2024 through April 2025 from Argentina, the UK, and the US. Pooled vaccine effectiveness against RSV-associated LRTI hospitalization was 82% (95% CI, 81%-82%; 3 studies, 4397 participants; I 2 = 0%) in infants from birth to 3 months and 78% (95% CI, 70%-84%; 6 studies, 3008 participants; I 2 = 18.7%) in infants from birth to 6 months, when mothers were vaccinated 14 days or more before delivery. Conclusions and Relevance The results of this systematic review and meta-analysis suggest that postimplementation data support the effectiveness of RSVpreF in pregnancy for the prevention of RSV-associated LRTI hospitalization during the first 6 months of life. The results support the introduction of RSVpreF into routine antenatal immunization programs.