Influenza A(H3N2) Subclade K (J.2.4.1): Molecular Characterization, Antigenic Divergence, and Global Spread During the 2025/26 Season.

Background

Influenza A(H3N2) continues to evolve rapidly, frequently eroding population immunity and challenging seasonal vaccine strain selection. During the 2025/26 season, the A(H3N2) subclade K (J.2.4.1) expanded quickly across multiple regions and showed evidence of antigenic divergence in standard assays.

Methods

In this study, we combined phylogenetic analyses of hemagglutinin (HA) and neuraminidase (NA) sequences with a systematic synthesis of recent peer-reviewed studies and official surveillance reports to comprehensively define the molecular profile and early epidemiological dynamics of subclade K.

Results

Our phylogenetic reconstructions of HA and NA genes confirmed the emergence of a coherent and recently diversified lineage characterized by coordinated evolution of surface glycoproteins and broad geographic representation during 2025. Integration of molecular, temporal, and surveillance evidence further supported rapid expansion with limited early regional structuring. Antigenic analyses reported in peer-reviewed studies described reduced haemagglutination inhibition reactivity to vaccine reference antisera for many subclade K viruses, whereas vaccine effectiveness (VE) estimates from multiple settings remained moderate.

Conclusions

Overall, the available genetic, antigenic, and epidemiological evidence indicates that subclade K represents a recently diversified A(H3N2) lineage associated with rapid international spread during the 2025/26 season, highlighting the importance of integrated HA/NA genomic surveillance and timely antigenic characterization to support evidence-based vaccine strain selection.