Efficacy, Effectiveness, and Immunogenicity of the Respiratory Syncytial Virus Prefusion F Vaccine Administered During Pregnancy: Protocol for a Living Systematic Review and Meta-Analysis

Abstract

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease in infants, with the highest burden in the first 6 months of life. Maternal immunization with the bivalent (RSV-A and RSV-B) prefusion F (RSVPreF) protein subunit vaccine (ABRYSVO) is a recently recommended strategy for preventing RSV-related outcomes in infants. First licensed for use in pregnancy in 2023, the RSVPreF vaccine demonstrated efficacy in a single pivotal randomized trial (Maternal Immunization Study for Safety and Efficacy; MATISSE); postlicensure real-world evidence on vaccine effectiveness across settings, seasons, and subgroups and on antibody durability and transplacental transfer remains limited and has not been synthesized in a continuously updated framework, motivating this review. Objective This living systematic review and meta-analysis will synthesize emerging postlicensure data on the efficacy, effectiveness, and immunogenicity of the RSVPreF vaccine in real-world settings. Methods We will conduct, in real time, a living systematic review and meta-analysis following Cochrane methods and PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) guidance, including randomized clinical trials and postlicensure real-world studies (eg, cohort, case-control, test-negative, and quasi-experimental studies). Primary objectives are evaluation of vaccine efficacy and effectiveness in preventing RSV-specific and all-cause respiratory disease and immunogenicity in infants and pregnant individuals. Vaccine effectiveness outcomes include RSV laboratory-confirmed infection, RSV acute respiratory illness, RSV lower respiratory tract disease, RSV hospitalization, RSV complications, all-cause lower respiratory tract disease and hospitalization, and antibiotic use in infants with RSV infection. Immunogenicity outcomes include maternal neutralizing antibody titers, maternal-infant transfer ratios, infant titers over time, and RSV viral load. We will search MEDLINE, Embase, the Cochrane Library, LILACS, Science Citation Index Expanded, Chinese biomedical and citation databases, clinical trial registries from January 2023 onward with no language restrictions, updating at least monthly. Two investigators will independently select studies, extract data, and assess risk of bias. Adjusted estimates will be standardized to vaccine efficacy and effectiveness. Certainty will be graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results This living systematic review was funded in June 2025. Searches began in January 2023 and will continue with surveillance updates at least monthly until April 2028. As of January 2026, 837 records were screened, 105 (12.5%) were assessed in full text, and 12 (1.4%) met the inclusion criteria, of which 10 (1.2%) contributed extractable data. Data collection and analysis are ongoing and displayed on an interactive dashboard. Findings will be disseminated through peer-reviewed publications, conferences, and a real-time dashboard, with the first effectiveness estimates available in July 2026. Conclusions This living systematic review and meta-analysis will provide a continuously updated synthesis of real-world evidence on maternal RSVPreF vaccination to inform clinical and policy decisions.