Bivalent RSV prefusion vaccine effectiveness against hospitalisation in older adults: meta-analysis of case–control studies in England, Wales, Scotland, and Northern Ireland

Background: Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In 2023, the RSVpreF vaccine was licenced and recommended for adults through the UK's national immunisation programmes. Real-world evidence on vaccine effectiveness (VE) across different populations and healthcare settings is limited. Methods: We conducted a retrospective, multi-nation, test-negative design analysis to evaluate RSVpreF VE against hospitalisation in adults aged 74-79 years across England, Wales, Scotland, and Northern Ireland during the 2024-25 RSV season. Laboratory testing, admission, and vaccination data were linked at the individual patient level. Eligible cases were hospitalised individuals with laboratory-confirmed RSV, and controls were RSV-negative hospitalised patients; SARS-CoV-2- and influenza-positive controls were excluded in the primary analysis. Nation-specific VE estimates were derived using multivariable logistic regression, adjusted for epidemiological week of specimen collection, and combined using fixed-effects meta-analysis with inverse-variance weighting. Sensitivity analyses included redefinition of controls and leave-one-nation-out analyses. Findings: = 0%). VE estimates from sensitivity analyses were robust to the inclusion of vaccine-preventable respiratory infection controls and adjustment for vaccination status. Leave-one-nation-out sensitivity analysis showed that excluding England increased pooled VE to 81% (66-89), whereas exclusion of NI, Scotland, or Wales had minimal impact (75%, 68-80 to 69-80). Interpretation: RSVpreF vaccination provides high real-world protection against RSV-related hospitalisation in adults across the UK. Funding: This study received no specific funding.