A MODIFIED mRNA influenza vaccine delivered superior efficacy with more reactogenicity than a licensed quadrivalent comparator.
Higher Relative Efficacy Against Influenza Like Illness
In this randomized Phase III trial, investigators assigned 18,476 healthy adults between 18 and 64 years of age to receive either a quadrivalent modified mRNA influenza vaccine or a licensed inactivated quadrivalent influenza vaccine during the 2022 to 2023 influenza season in the United States, South Africa, and the Philippines. The primary end point was relative efficacy, defined as reduction in laboratory confirmed influenza associated with influenza like illness at least 14 days after vaccination. The modified mRNA influenza vaccine reduced influenza like illness by 34.5% compared with the standard vaccine, based on 57 cases in the modified mRNA group and 87 cases in the control group. This result met prespecified criteria for both noninferiority and superiority.
Immunogenicity and Safety of the Modified mRNA Influenza Vaccine
Hemagglutination inhibition assay results showed noninferior antibody responses against influenza A strains, including A/H3N2 and A/H1N1, while noninferiority criteria were not met for B strains. Most virologically confirmed cases during the study period were due to influenza A, with very few B strain infections detected. Reactogenicity was common in both vaccine groups and was predominantly mild or moderate, but local and systemic events were more frequent after the modified mRNA influenza vaccine. Overall local reactions occurred in 70.1% of participants in the modified mRNA group and 43.1% in the control group. Systemic events were reported in 65.8% and 48.7% of participants respectively.
Clinical Implications for Seasonal Influenza Prevention
Fever occurred in 5.6% of participants who received the modified mRNA influenza vaccine and 1.7% of those who received the licensed inactivated vaccine. Despite these higher rates of reactogenicity, adverse event profiles were otherwise similar between groups over six months of follow up. These findings suggest that a modified mRNA influenza vaccine platform can deliver enhanced protection against circulating influenza A strains in adults, with an acceptable tolerability profile for most recipients. For clinicians, the results highlight a potential future option in seasonal influenza vaccination strategies that balances improved efficacy with increased but mostly manageable short term local and systemic reactions.
Reference: Fitz-Patrick D et al. Efficacy, Immunogenicity, and Safety of Modified mRNA Influenza Vaccine. N Engl J Med. 2025;393(20):2001-2011.
