Immunogenicity and safety of two priming doses of an MF59-adjuvanted cell-based H5N8 influenza vaccine in healthy persons aged ≥18 years

Background Increased transmission of avian influenza from animals to humans has elevated the risk of an H5 pandemic. Methods This phase 2, randomized, observer-blind, multi-center trial assessed the immunogenicity and safety of homologous priming with an MF59-adjuvanted, cell-based H5N8 A/Astrakhan/3212/2020 clade 2.3.4.4b vaccine (aH5N8c). We enrolled adults age ≥18 years, equally stratified into 18–64 (including a poultry-worker subset) and ≥65 year cohorts. Primary and secondary outcomes were homologous antibody responses against H5N8 measured in all participants by hemagglutination inhibition (HI) and in a subset by microneutralization (MN) assays on Days 1, 22, and 43. Solicited adverse events (AEs) were monitored for 7 days post-vaccination, with unsolicited AEs tracked throughout Day 43. Results 239 participants were vaccinated (18–64 years, n = 121; ≥65 years, n = 118). At Day 43 (21 days post second aH5N8c dose), geometric mean fold increases (GMFI) were 13.7 for the 18–64 cohort and 10.2 for the ≥65 cohort. HI seroconversion rates were 75.8% (95% CI 66.1–83.8%) for the 18–64 cohort and 71.0% (61.1–79.6%) for the ≥65 cohort. HI titers ≥1:40 were achieved in 75.8% (66.1–83.8%) and 73.0% (63.2–81.4%) of participants, respectively. MN seroconversion rates were 80.6% (68.6–89.6%) and 70.0% (56.8–81.2%), while MN titers ≥1:40 were 83.9% (72.3–92.0%) and 86.7% (75.4–94.1%), respectively. No notable differences in immune responses by poultry worker status were observed. Most solicited AEs were mild or moderate, resolving within 3 days. Unsolicited AEs were reported by 16.7% participants by Day 43. Conclusion These data support the use of the MF59-adjuvanted, cell-based monovalent H5N8 vaccine as a public health intervention against H5 influenza.