Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults

作者：Eleanor Wilson, Jaya Goswami, Abdullah H Baqui, Pablo Alexis Doreski, Gonzalo Perez-Marc, Khalequ Zaman, Jorge Monroy, C.J. Duncan, Mugen Ujiie, Mika Rämet, Lina Pérez–Breva, Ann R. Falsey, Edward E. Walsh, Rakesh Dhar, Lauren Wilson, Jiejun Du, Parinaz Ghaswalla, Archana Kapoor, Lan Lan, Shraddha Mehta, Runa Mithani, Catherine A. Panozzo, Alana K. Simorellis, Barbara J. Kuter, F. Schödel, Wenmei Huang, Caroline Reuter, Karen Slobod, Sonia Stoszek, Christine A. Shaw, Jacqueline M. Miller, Rituparna Das, Grace Chen · 发表于：New England Journal of Medicine · 年份：2023 · DOI：10.1056/nejmoa2307079 · 被引用次数：498 · 研究领域：Respiratory viral infections research、COVID-19 Clinical Research Studies、Animal Virus Infections Studies

BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation. METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 μg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed. RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and...