Influenza A(H3N2) Subclade K: Epidemiology, Molecular Evolution and Vaccine Effectiveness in Europe

Background: Influenza A(H3N2) viruses remain a major public health concern due to their rapid antigenic evolution and association with severe disease, particularly among high-risk populations. During the 2025–2026 influenza season, a marked epidemiological shift was observed in Europe, with the emergence and predominance of the A(H3N2) subclade K (J.2.4.1). Objectives: This narrative review aims to provide an integrated overview of the epidemiology, evolutionary dynamics, and public health implications of subclade K, with a particular focus on its impact on vaccine effectiveness, in comparison with the 2024–2025 influenza season. Methods: A non-systematic literature review was conducted using major scientific databases and official public health sources, including WHO and ECDC reports. Recent surveillance data, genomic analyses, and epidemiological updates were included. Given the rapidly evolving evidence base, selected preprint studies were also considered and interpreted with caution. Results: The 2025–2026 influenza season in Europe was characterized by a relative genetic convergence, with subclade K accounting for the majority of A(H3N2) sequences. This variant demonstrated a clear selective advantage and was associated with an earlier and more intense epidemic peak. Molecular analyses indicate the accumulation of multiple mutations in the hemagglutinin protein, particularly within key antigenic sites, contributing to immune escape. These evolutionary changes have important implications for vaccine effectiveness, with current estimates suggesting moderate protection against infection but preserved effectiveness against severe outcomes. Antigenic mismatch, manufacturing constraints, and host-related factors further contribute to reduced vaccine performance. Conclusions: The emergence and rapid spread of subclade K highlight the dynamic nature of influenza virus evolution and its impact on public health. Continuous genomic surveillance and timely vaccine updates remain essential. Despite suboptimal effectiveness against infection, influenza vaccination continues to provide significant protection against severe disease and should remain a cornerstone of prevention strategies.