Efficacy, Immunogenicity, and Safety of Modified mRNA Influenza Vaccine
David Fitzpatrick, Donald S McVinnie, Lisa A. Jackson, Graham Crowther, Anita Geevarughese, Kevin D. Cannon, Lazaro M. Garcia, Yanely Pineiro Puebla, Zhuobiao Yi, Luke Cunliffe, Alok Maniar, Agnieszka Zareba, Claudia Ana Ianos, Emily Gomme, Kenneth Koury, Pirada Suphaphiphat Allen, Annaliesa S. Anderson, Alejandra Gurtman, Kelly Lindert
Abstract
BACKGROUND: Influenza remains a major health burden despite the use of licensed vaccines. Nucleoside-modified messenger RNA (modRNA) influenza vaccines have shown promising immunogenicity against influenza and an acceptable safety profile in a phase 1-2 trial. METHODS: In this phase 3 trial, we randomly assigned healthy adults between the ages of 18 and 64 years to receive either a quadrivalent modRNA influenza vaccine (modRNA group) or a licensed inactivated quadrivalent influenza vaccine (control group) during the 2022-2023 influenza season in the United States, South Africa, and the Philippines. The primary end point was relative efficacy, defined by the reduction in the percentage of participants with laboratory-confirmed influenza associated with influenza-like illness at least 14 days after vaccination with the modRNA vaccine, as compared with the control vaccine, and analyzed for noninferiority and superiority. Immunogenicity was evaluated by means of a hemagglutination inhibition (HAI) assay. We assessed reactogenicity within 7 days after vaccination, adverse events through 1 month, and serious adverse events through 6 months. We assessed vaccine efficacy, immunogenicity, and safety in the modRNA group. RESULTS: A total of 18,476 participants underwent randomization: 9225 were assigned to receive the modRNA vaccine and 9251 to receive the control vaccine. The relative efficacy of the modRNA vaccine as compared with the control vaccine against influenza-like illness was 34.5% (95% confidence interval [CI], 7.4 to 53.9) on the basis of 57 cases in the modRNA group and 87 cases in the control group, a finding that met the criteria for both noninferiority and superiority. Cases of influenza-like illness were caused by A/H3N2 and A/H1N1 strains but almost no B strains. The noninferiority of the antibody response on HAI assay was shown for influenza A strains but not for B strains. Primarily mild or moderate reactogenicity was observed in both vaccine groups but was reported more frequently in the modRNA group (overall local reactions, 70.1% vs. 43.1%; overall systemic events, 65.8% vs. 48.7%). Fever occurred in 5.6% of the participants in the modRNA group and in 1.7% of those in the control group. Adverse event profiles were similar in the two groups. CONCLUSIONS: : Human clinical trial of a nucleoside-modified mRNA influenza vaccine.