Influenza A subclade K viruses caused high infection rates in the 2025/2026 Northern Hemisphere season, raising concerns about antigenic drift and reduced vaccine effectiveness. We measured antibody responses in matched human pre- and post-vaccination sera against a vaccine-like as well as subclade K isolates. Pre-existing immunity to subclade K variants was noted with seasonal influenza vaccination boosting titers two-fold against subclade K and three-fold against the vaccine-like strain, indicating little antigenic drift. These data contrast ferret-based predictions of marked antigenic drift.
Keywords: and/or cross-reactive immunity; antigenic drift; hemagglutination inhibition antibodies; influenza A H3N2 subclade K; neutralizing antibodies; vaccine-induced immunity.