• Eleanor Wilson, Jaya Goswami, Abdullah H Baqui, Pablo A Doreski, Gonzalo Perez-Marc, Khalequ Zaman, Jorge Monroy, DuncanChristopher J ACJAFrom Moderna, Cambridge, MA (E.W., J.G., R. Dhar, L.W., J.D., P.G., A.K., L.L., S.M., R.M., C.A.P., A.K.S., B.J.K., F.S., W.H., C.R., K.S., S.K.S., C.A.S., J.M.M., R. Das, G.L.C.); Johns Hopkins Bloomberg School of Public Health, B, 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, Florian Schödel, Wenmei Huang, Caroline Reuter, Karen Slobod, Sonia K Stoszek, Christine A Shaw, Jacqueline M Miller, Rituparna Das, Grace L Chen, and ConquerRSV Study Group.
• From Moderna, Cambridge, MA (E.W., J.G., R. Dhar, L.W., J.D., P.G., A.K., L.L., S.M., R.M., C.A.P., A.K.S., B.J.K., F.S., W.H., C.R., K.S., S.K.S., C.A.S., J.M.M., R. Das, G.L.C.); Johns Hopkins Bloomberg School of Public Health, Baltimore (A.H.B.); Fundación Respirar-Vaccine Research Division (P.A.D.) and Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich (G.P.-M.) - both in Buenos Aires; International Center for Diarrheal Disease Research, Dhaka, Bangladesh (K.Z.); Clinical Site Partners, Winter Park, FL (J.M.); Translational and Clinical Research Institute, Newcastle University, and the National Institute for Health and Care Research Newcastle Clinical Research Facility, Newcastle upon Tyne Hospitals NHS Foundation Trust - both in Newcastle upon Tyne, United Kingdom (C.J.A.D.); Center Hospital of the National Center for Global Health and Medicine, Tokyo (M.U.); Rokotetutkimusklinikka, Järvenpää, and Finnish Vaccine Research, Tampere - both in Finland (M.R.); Vaccine Research-Foundation for the Promotion of Health and Biomedical Research of the Valencia Region (FISABIO) Public Health, Valencia, Spain (L.P.-B.); and the University of Rochester, Rochester, NY (A.R.F., E.E.W.).
• N. Engl. J. Med. 2023 Dec 14; 389 (24): 223322442233-2244.

BackgroundRespiratory 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.MethodsIn 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.ResultsOverall, 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 B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group.ConclusionsA single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).Copyright © 2023 Massachusetts Medical Society.

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