Understanding the emergence of the influenza A/H3N2 K subclade in its historical and evolutionary context

The emergence in 2025/26 of the influenza A/H3N2 K substrain (H3N2/K) was the cause of significant public health concern. This genetically divergent virus was assessed to have a strongly decreased reactivity to contemporary vaccine strains. Respectively prolonged and early influenza seasons in the Southern and Northern Hemispheres contributed to concerns about vaccine efficacy. Here we retrospectively assessed the genetic and antigenic properties of this virus, combining epidemiological surveillance data, computational antigenic analysis, and serological data using samples from a well-stratified UK cohort. In contrast to initial indications, we found that despite the genetic distinctiveness of H3N2/K the virus had undergone limited antigenic change, suggesting that its emergence was instead the result of selection for non-antigenic properties. We confirmed previous results showing that contemporary vaccines produced an enhanced neutralising response to H3N2/K but, in a stratified serological analysis, showed that responses to the J and K substrains were age-dependent, largely driven by patterns of vaccination. Our results have implications for antigenic surveillance and for public communication strategies in future influenza seasons.