Assessment of human immunity to A/H3N2 influenza subclade K during 2025 emergence
More about Open Access at the CrickAuthors list
Ruth Harvey Ceilidh Welsh Alex Byrne David Greenwood Phoebe Stevenson-Leggett Monica Galiano Dalan Bailey Yung-Wai Chan Jacob Boateng Hannah Wolmuth-Gordon Heather Whitaker Kevin E Brown Anna Jeffery-Smith Alex Allen Gayatri Amirthanlingam Even Fossum Elisabeth Lea Vikse Andreas Rohringer Olav Hungnes Karoline Bragstad Charles Swanton Bryan Williams Sonia Gandhi Steve Gamblin Edward Carr Nicola Lewis Emma Wall Mary Wu Crick Serology Pipeline Legacy Investigators
Toggle all authors (30)
Abstract
BACKGROUND: Seasonal influenza causes significant morbidity and mortality annually. In 2025, the genetically divergent A/H3N2 K subclade (J.2.4.1) emerged with substantial haemagglutinin mutations. However, despite suggested antigenic escape, UK vaccine effectiveness estimates and epidemiological data demonstrated a relatively normal influenza season across 2025-26. We examined neutralising antibody responses in human cohorts to investigate existing and vaccine-induced immunity to K clade viruses. METHODS: We characterised the antigenic relationships of a selection of A/H3N2 viruses spanning recent evolution including a subclade K virus using antigenic cartography, followed by serological antibody profiling of four human cohorts from the United Kingdom and Norway using microneutralisation (MN) and haemagglutination inhibition (HAI) assays. FINDINGS: Antigenic cartography from single-infection ferret antisera suggests significant antigenic drift from the vaccine strains. MN and HAI titres from 243 individuals across 4 human cohorts (ages 1-105 years) were measured for comparison. The 2025/26 Northern Hemisphere seasonal inactivated egg-derived trivalent influenza vaccine (eTIV, with J.2 A/H3N2) significantly boosted MN and HAI titres against all A/H3N2 viruses tested, including a subclade K virus (p < 0.001). Furthermore, serological profiles of cohorts stratified by age groups (≤5, >5-≤15, >20-≤25, >25-<60, and ≥60) showed pre-existing reactivity against the emergent subclade K viruses, with minimal inter-age variation, suggesting there was not an immunity gap within particular age groups. INTERPRETATION: The 2025/26 seasonal inactivated eTIV vaccine effectively boosted neutralising titres despite substantial genetic and antigenic drift. Human serological profiling should be included in risk assessments and continued surveillance. FUNDING: The Francis Crick Institute with core funding from Cancer Research UK, UK Medical Research Council, and Wellcome Trust; UK Research and Innovation and UK Medical Research Council; National Institute for Health Research University College London Hospitals Biomedical Research Centre; UK Health Security Agency; Norwegian Institute of Public Health.
Full text links
Publisher website (DOI)
10.1016/j.ebiom.2026.106332
Figshare
View on figshare
Europe PubMed Central
42276011
Pubmed
42276011
Data and code
Keywords
Related topics
Type of publication
