Efficacy and Safety of an mRNA Seasonal Influenza Vaccine in Adults

Efficacy and Safety of an mRNA Seasonal Influenza Vaccine in Adults Published May 6, 2026 N Engl J Med 2026;394:1803-1813 DOI: 10.1056/NEJMoa2516491 Abstract Background Seasonal influenza causes substantial illness and death in adults 50 years of age or older, even with current vaccines. An investigational messenger RNA (mRNA)–based vaccine called mRNA-1010 encodes hemagglutinin glycoproteins from World Health Organization–recommended influenza strains. Methods In this phase 3, double-blind, active-controlled trial, we randomly assigned adults 50 years of age or older to receive trivalent mRNA-1010 (37.5 μg, which includes 12.5 μg of each strain) or a licensed standard-dose comparator. The primary efficacy end point was relative vaccine efficacy against reverse-transcriptase–polymerase-chain-reaction (RT-PCR)–confirmed, protocol-defined influenza-like illness caused by influenza A or B, from at least 14 days after vaccination through the end of the influenza season. Hypothesis testing was conducted hierarchically to assess noninferiority (lower boundary of the 95% confidence interval [CI], >−10%), superiority (lower boundary of the 95% CI, >0%), and a higher level of superiority (lower boundary of the 95% CI, >9.1%). Results A total of 40,703 participants received mRNA-1010 (20,350 participants) or the standard-dose comparator (20,353 participants); the median follow-up was 181 days (range, 1 to 227). RT-PCR–confirmed, protocol-defined influenza-like illness was observed in 411 of 20,179 recipients of mRNA-1010 (2.0%) and 557 of 20,124 recipients of the standard-dose comparator (2.8%), which corresponds to a relative vaccine efficacy of 26.6% (95% CI, 16.7 to 35.4), thereby meeting the criteria for noninferiority, superiority, and higher-level superiority. Solicited adverse reactions were more frequent with mRNA-1010 than with the standard-dose comparator (injection-site pain in 65.8% vs. 29.8%, fatigue in 45.1% vs. 20.3%, headache in 37.8% vs. 18.0%, and myalgia in 35.4% vs. 11.6%); most reactions were mild to moderate and transient. Serious adverse events were reported in 2.2% of the recipients of mRNA-1010 (with three events considered by the investigator to be vaccine-related) and in 1.9% of the recipients of the standard-dose comparator (with two events considered by the investigator to be vaccine-related). Conclusions In this trial, mRNA-1010 was superior to standard-dose licensed vaccines for prevention of RT-PCR–confirmed, protocol-defined influenza-like illness in adults 50 years of age or older. Solicited adverse reactions were more frequent with mRNA-1010. (Funded by Blackstone Life Sciences and Moderna; Fluent ClinicalTrials.gov number, NCT06602024.) Are you a member of an institution such as a university or hospital?Learn more about Institutional Access Notes A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Supported by Blackstone Life Sciences and Moderna. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank the participants in the trial and their families; the members of the data and safety monitoring board for their hard work, support, and guidance of the trial; Agi Buchanan, M.D., Ph.D., Andrei Avanesov, Ph.D., Ren Chen, Ph.D., Haritha Singireddy, M.S., Brianna Fidler, M.A., Elissa Malkin, D.O., M.P.H., Chelsea Canan, Ph.D., M.P.H., and Peg Mutty, B.S., of Moderna, for helpful discussions; Alana Simorellis, Ph.D., of Moderna, for writing and editorial support with an earlier version of the manuscript; and Aliscia Daniels, Ph.D., of MEDiSTRAVA, for medical writing and editorial assistance with an earlier version of the manuscript, in accordance with Good Publication Practice (GPP3) guidelines, funded by Moderna, and under the direction of the authors. Supplementary Material Information & Authors Information Published In Copyright Copyright © 2026 Massachusetts Medical Society. All rights reserved. For personal use only. Any commercial reuse of NEJM Group content requires permission. History Published online: May 6, 2026 Published in issue: May 7, 2026 Topics Authors Metrics & Citations Metrics Altmetrics Citations Export citation Select the format you want to export the citation of this publication. Cited by - Moderna’s mRNA flu vaccine outperforms standard shot, study finds, BMJ, 393, (s895), (2026).https://doi.org/10.1136/bmj.s895 Loading...