Early circulation of influenza A(H3N2) subclade K: antigenic drift and vaccine effectiveness

The 2025–2026 influenza season in the Northern Hemisphere started earlier than in recent seasons, with a marked increase in influenza A activity. A recent study from England by Kirsebom et al. [1] reported that influenza A(H3N2) subclade K (formerly J.2.4.1) dominated early-season circulation and was accompanied by increased hospitalizations and high test positivity rates, particularly among school-aged children [2]. Similar trends have been observed across the European Union (EU)/European Economic Area and Canada, where subclade K has contributed to rising influenza activity in recent weeks [3,4]. In the Western Pacific Region, subclade K accounts for 89% of reported H3N2 sequences [5].

Early antigenic evaluations indicate that circulating subclade K viruses show reduced reactivity to the Northern Hemisphere 2025–2026 vaccine reference strain. These findings are consistent with World Health Organization reports of ongoing antigenic drift among contemporary A(H3N2) viruses [1,6]. Nonetheless, vaccine effectiveness (VE) against medically attended influenza and hospitalization remained within expected ranges in England (children/adolescents, 72%–75%; adults, 32%–39%) during the early postvaccination period. Complementary data from the European Centre for Disease Prevention and Control’s Vaccine Effectiveness, Burden and Impact Studies program showed an overall VE of 52% against outpatient H3N2 infection across nine EU countries [3]. Canadian data also reported a VE of 40% against medically attended A(H3N2) illness, with subclade K-specific VE estimated at 37% during November 2025–January 2026 [4,7]. This contrast underscores the importance of interpreting laboratory evidence of antigenic drift in the context of real-world VE. Although hemagglutination inhibition assays using ferret antisera are central to strain selection, they may not fully predict population-level clinical protection, particularly in atypical seasons [8].

Several limitations should be considered. First, these early VE estimates do not capture possible waning of effectiveness later in the season [1,3]. Second, the wide confidence intervals for A(H3N2)-specific VE in adults likely reflect limited viral subtyping in older age groups. In addition, antigenic characterization based on a relatively small subset of viruses may not capture the full diversity of circulating strains. Geographic representativeness is also limited by reliance on secondary care samples with batch referrals and variable site adherence [1].

Overall, early VE findings provide reassuring evidence of vaccine protection against severe influenza outcomes despite laboratory evidence of reduced reactivity in emerging A(H3N2) variants. These findings highlight the importance of ongoing genomic surveillance and continued VE monitoring throughout the season during atypical influenza activity. Given the rapid circulation of this variant, coordinated international surveillance and response measures are particularly important. In addition, reinforced vaccination campaigns for high-risk populations and improved public communication strategies are essential to maintaining confidence in influenza vaccination. For healthcare systems, surge-capacity planning, including pediatric bed expansion and provision of post-exposure antiviral prophylaxis to frontline staff within 48 hours of exposure, are key measures for protecting healthcare workers [5]. At the community level, healthcare systems should strengthen communication with long-term care facilities and schools regarding early symptom recognition and isolation protocols, while maintaining adequate stockpiles of personal protective equipment and antiviral medications for sustained response periods.

HIGHLIGHTS

• The 2025–2026 influenza season began unusually early in the Northern Hemisphere, with dominance of influenza A(H3N2) subclade K.

• Early antigenic analyses show reduced reactivity between subclade K viruses and the 2025–2026 vaccine reference strain.

• Despite antigenic drift, vaccine effectiveness remains reassuring across multiple studies, and vaccination remains the most effective tool for protection.

Graphical abstract