Inactivated Zoonotic Influenza A(H5N8) Vaccine Induces Humoral and Cell-mediated Immune Responses Against Highly Pathogenic Avian Influenza Clade 2.3.4.4b A(H5N1) Viruses

In 2023, Finland faced an outbreak of highly pathogenic clade 2.3.4.4b A(H5N1) avian influenza, spreading from wild birds to fur farms. Vaccinations of at-risk individuals began in June 2024 using the MF59-adjuvanted inactivated A(H5N8) vaccine (Seqirus; A/Astrakhan/3212/2020, clade 2.3.4.4b). We assessed virus-specific antibody (n=39) and T-cell (n=18) responses. Vaccination elicited functional antibodies against the vaccine virus and two heterologous clade 2.3.4.4b strains associated with outbreaks on Finnish fur farms and dairy cattle in the U.S. Among previously unvaccinated individuals, seroprotection rates against the vaccine virus were 83% (95% CI 70–97%) by microneutralization assay (titer ≥20) and 97% (90–100%) by hemagglutination inhibition assay (titer ≥40). In all those previously vaccinated against avian influenza, a single dose induced seroprotection. A(H5N8)-specific memory CD4+ T-cell responses were detectable, with ~5-fold increase in IFN-γ secretion after two doses. These results demonstrate that the vaccine likely provides cross-protection against circulating H5 clade 2.3.4.4b viruses.