A Phase 1/2 Dose-Ranging Safety and Immunogenicity Study of mRNA-Based Candidate Pandemic Influenza Vaccines in Healthy Adults

Abstract Background Influenza A viruses pose a persistent pandemic threat. We report safety, reactogenicity, and immunogenicity findings for mRNA-1018 pandemic influenza vaccine candidates from a phase 1/2 study in healthy adults. Methods In part A, participants were randomized to receive 1 of 4 mRNA-1018 candidates at 1 of 3 dose levels across 2 influenza A groups: (1) H5N8/H5-only or (2) H7N9/H7-only. Part B participants were randomized to receive H5-only-CG. The primary objectives were to evaluate the safety and reactogenicity. The secondary objectives included evaluation of humoral immunogenicity through day 205 by hemagglutination inhibition (HAI), neuraminidase inhibition, and microneutralization assays. Results Parts A and B comprised 1195 and 304 dosed participants, respectively. Overall, solicited local adverse reactions (ARs) within 7 days of vaccination occurred in 76.8% of participants across vaccine candidates and dose levels, most commonly injection-site pain. Solicited systemic ARs were reported in 62.8% of participants, most frequently fatigue and headache. Postvaccination immune responses, assessed absolutely, by HAI titers and dynamically, by seroconversion rates, tended to increase with vaccine dose. H5-based candidates induced stronger strain-specific HAI. Conclusions Vaccine candidates were sufficiently well tolerated and immunogenic. Further development of mRNA pandemic influenza vaccines is warranted. Clinical Trials Registration. NCT05972174