Immunogenicity of influenza split vaccine for 2025/26 season in Japan using a mouse model

Seasonal influenza viruses continuously evolve, and the composition of the seasonal influenza vaccine is reviewed by the World Health Organization twice a year due to antigenic drift in the viral hemagglutinin (HA) protein. A timely assessment of how well vaccine-induced antibodies react to circulating viruses remains warranted. Here, immunogenicity of reference split vaccines for the 2025/26 season in Japan was analyzed in a mouse model using a microneutralization (MN) antibody assay against circulating A(H1N1)pdm09, A(H3N2), and B/Victoria-lineage viruses. In Japan, the vaccine used in the 2025/26 season consisted of three virus strains: A/Victoria/4897/2022 (IVR-238) (H1N1)pdm09, A/Perth/722/2024 (IVR-262) (H3N2), and B/Austria/1359417/2021 (BVR- 26). Reduced MN reactivity was observed against the tested circulating viruses, including A/Tokyo/EIS11-980/2025 (H1N1)pdm09 (HA subclade D.3.1), A/Tokyo/EIS13-029/2025 (H3N2) (HA subclade J.2.3), A/Tokyo/EIS13-355/2025 (H3N2) (HA subclade K), and B/Kanagawa/AC2414/2025 (B/Victoria lineage, HA subclade C3.1), with MN titers at least four-fold lower than those for the corresponding vaccine strains. These isolates had several amino acid substitutions at the antigenic or glycosylation sites in HA compared to the vaccine strains. These findings provide early laboratory indication of decreased immunogenicity of the vaccine against specific circulating viruses during the 2025/26 season in Japan.