tetano
Editor, Senior Moderator
EBioMedicine
. 2026 Jun 11:129:106332.
doi: 10.1016/j.ebiom.2026.106332. Online ahead of print.
Assessment of human immunity to A/H3N2 influenza subclade K during 2025 emergence
Ruth Harvey[SUP] 1 [/SUP], Ceilidh Welsh[SUP] 2 [/SUP], Alexander Mp Byrne[SUP] 1 [/SUP], David Greenwood[SUP] 2 [/SUP], Phoebe Stevenson-Leggett[SUP] 3 [/SUP], Monica Galiano[SUP] 1 [/SUP], Dalan Bailey[SUP] 4 [/SUP], Yung-Wai Chan[SUP] 5 [/SUP], Jacob Boateng[SUP] 5 [/SUP], Hannah Wolmuth-Gordon[SUP] 5 [/SUP], Heather Whitaker[SUP] 6 [/SUP], Kevin E Brown[SUP] 5 [/SUP], Anna Jeffery-Smith[SUP] 5 [/SUP], Alex Allen[SUP] 5 [/SUP], Gayatri Amirthanlingam[SUP] 5 [/SUP], Even Fossum[SUP] 7 [/SUP], Elisabeth Lea Vikse[SUP] 7 [/SUP], Andreas Rohringer[SUP] 7 [/SUP], Olav Hungnes[SUP] 7 [/SUP], Karoline Bragstad[SUP] 7 [/SUP], Charles Swanton[SUP] 8 [/SUP], Bryan Williams[SUP] 9 [/SUP], Sonia Gandhi[SUP] 8 [/SUP], Steve Gamblin[SUP] 2 [/SUP], Edward J Carr[SUP] 10 [/SUP], Nicola S Lewis[SUP] 11 [/SUP], Emma C Wall[SUP] 12 [/SUP], Mary Y Wu[SUP] 13 [/SUP]; Crick Serology Pipeline; Legacy Investigators
Collaborators, Affiliations
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.
Keywords: Antigenic cartography; H3N2; Haemagglutination inhibition; Human serology; Neutralising antibodies; Seasonal influenza; Subclade K; Vaccine.
. 2026 Jun 11:129:106332.
doi: 10.1016/j.ebiom.2026.106332. Online ahead of print.
Assessment of human immunity to A/H3N2 influenza subclade K during 2025 emergence
Ruth Harvey[SUP] 1 [/SUP], Ceilidh Welsh[SUP] 2 [/SUP], Alexander Mp Byrne[SUP] 1 [/SUP], David Greenwood[SUP] 2 [/SUP], Phoebe Stevenson-Leggett[SUP] 3 [/SUP], Monica Galiano[SUP] 1 [/SUP], Dalan Bailey[SUP] 4 [/SUP], Yung-Wai Chan[SUP] 5 [/SUP], Jacob Boateng[SUP] 5 [/SUP], Hannah Wolmuth-Gordon[SUP] 5 [/SUP], Heather Whitaker[SUP] 6 [/SUP], Kevin E Brown[SUP] 5 [/SUP], Anna Jeffery-Smith[SUP] 5 [/SUP], Alex Allen[SUP] 5 [/SUP], Gayatri Amirthanlingam[SUP] 5 [/SUP], Even Fossum[SUP] 7 [/SUP], Elisabeth Lea Vikse[SUP] 7 [/SUP], Andreas Rohringer[SUP] 7 [/SUP], Olav Hungnes[SUP] 7 [/SUP], Karoline Bragstad[SUP] 7 [/SUP], Charles Swanton[SUP] 8 [/SUP], Bryan Williams[SUP] 9 [/SUP], Sonia Gandhi[SUP] 8 [/SUP], Steve Gamblin[SUP] 2 [/SUP], Edward J Carr[SUP] 10 [/SUP], Nicola S Lewis[SUP] 11 [/SUP], Emma C Wall[SUP] 12 [/SUP], Mary Y Wu[SUP] 13 [/SUP]; Crick Serology Pipeline; Legacy Investigators
Collaborators, Affiliations
- PMID: 42276011
- DOI: 10.1016/j.ebiom.2026.106332
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.
Keywords: Antigenic cartography; H3N2; Haemagglutination inhibition; Human serology; Neutralising antibodies; Seasonal influenza; Subclade K; Vaccine.