A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy Adults

作者：Angela R Branche, Mark J. Mulligan, Alok Maniar, Orlando Puente, Islamiat Oladipupo, Graham Crowther, Agnieszka Zareba, Zhuobiao Yi, Ingrid L. Scully, Emily Gomme, Kenneth Koury, Nicholas Kitchin, Pirada Suphaphiphat Allen, Annaliesa S. Anderson, Alejandra Gurtman, Kelly Lindert · 发表于：Vaccines · 年份：2025 · DOI：10.3390/vaccines13040383 · 被引用次数：9 · 研究领域：Influenza Virus Research Studies、SARS-CoV-2 and COVID-19 Research、Respiratory viral infections research

Background/Objectives: Circulating influenza strains antigenically differing from vaccine antigens increase disease burden by decreasing vaccine efficacy. Nucleoside-modified mRNA (modRNA) influenza vaccines may facilitate rapid production allowing later antigen selection and improved antigenic similarity compared to circulating strains. We studied different influenza modRNA vaccine (IRV) formulations and dose levels. Methods: This phase 1/2 randomized study evaluated IRV safety/tolerability and immunogenicity in healthy 18- through 85-year-olds. Based on safety and immunogenicity for different IRV doses, schedules, and valencies versus the quadrivalent influenza vaccine (QIV; Fluzone High-Dose Quadrivalent, Sanofi Pasteur) in phase 1 (65–85-year-olds), quadrivalent IRV (qIRV) was further evaluated in 65- through 85-year-olds and 18- through 64-year-olds in phase 2, leading to phase 3 dose selection. Results: Phase 1 (65–85-year-olds) safety/tolerability and immunogenicity findings supported qIRV 30-µg and 60-µg phase 2 assessment (18–85-year-olds, N = 610). qIRV was well tolerated. Injection site pain was the most frequently reported local reaction. Reactogenicity event incidences ≤ 7 days postvaccination for qIRV were generally higher versus QIV, observed more frequently in 18- through 64-year-olds than 65- through 85-year-olds, and showed dose-related trends (60 μg > 30 μg). qIRV and QIV adverse event profiles in 65- through 85-year-olds were similar. There were higher ...