Efficacy and Safety of an mRNA Seasonal Influenza Vaccine in Adults.

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.).