Maternal respiratory syncytial virus vaccination for infant protection: updated systematic review and meta-analysis of efficacy, effectiveness, and safety

Background: Respiratory syncytial virus (RSV) is a major cause of severe illness in infants and young children. Method: We updated this systematic review to explore the efficacy, effectiveness and safety of authorised maternal RSV prefusion F (RSVpreF) vaccines for infant protection. We searched MEDLINE, Cochrane Library/Central, Embase and grey literature from 2000 to June 2025. We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs). Two independent authors performed screening, data extraction, and risk-of-bias assessment following standard methods. The PROSPERO registration number is CRD42023439128. Results: Meta-analyses of RCTs showed that maternal RSVpreF vaccines lowered medically attended RSV-related lower respiratory tract infections with vaccine efficacy of 68% (relative risk (RR) 0.32; 95% confidence interval (CI) 0.13 to 0.77, 2 trials; 7,656 participants; high certainty of evidence (CoE)), severe RSV-related lower respiratory tract infections with a vaccine efficacy of 84% (RR 0.16; 95% CI 0.07 to 0.36, 2 trials; 7,656 participants, high CoE) and RSV-related hospitalisations with a vaccine efficacy of 70% (RR 0.30; 95% CI 0.15 to 0.61, 1 trial; 7,148 participants, high CoE) in infants. There may be little to no difference in RSV-related mortality, all-cause mortality, vaccine-related serious adverse events, and intensive care admission. Requirements for invasive ventilation and duration of hospitalisation due to RSV disease were not reported by any trials. NRSIs suggested comparable effectiveness against hospitalisation, but certainty was very low (vaccine effectiveness of 72%; RR 0.28; 95% CI: 0.17 to 0.46, 3 NRSIs; 1,229 participants, very low CoE). Interpretation: Maternal RSVpreF vaccination reduced medically attended and severe RSV-LRTI and RSV-related hospitalisation in infants. No safety signals were identified. Further research is required to clarify the long-term effectiveness of vaccines.