Have there been any antigenic changes in 2025-2026 H3N2 strains affecting vaccine match?
Executive summary
Genetic and antigenic analyses from surveillance groups and recent papers show that H3N2 viruses acquired multiple mutations in 2024–2025 and a newly named “subclade K” (bearing ~7 key HA changes including T135K, K189R and N158D among others) emerged in the Southern Hemisphere and is now widespread, with in‑vitro data and early antigenic assays indicating reduced reactivity to the 2025–26 vaccine reference strains (reported by WHO/ECDC analyses and peer‑reviewed/ preprint studies) [1] [2] [3]. Early real‑world vaccine‑effectiveness data are limited but preliminary reports stress that vaccines may still protect against severe outcomes even when antigenic mismatch is observed in laboratory assays [2] [3].
1. A cluster of HA mutations changed the antigenic picture
Multiple independent substitutions at established H3N2 “cluster transition” positions — notably 135, 145, 158 and 189 — were documented during the NH 2024–25 season and continued into the SH 2025 season, producing viruses antigenically distinct from the vaccine reference J/J.2 strains (authors’ sequence analysis and surveillance summaries) [1]. Subclade K is defined by J.2.4‑defining changes (T135K + K189R) plus additional substitutions such as N158D, I160K and S144N, which lie around the hemagglutinin receptor binding region and have known roles in antigenic drift [2] [1].
2. Laboratory antigenic data indicate reduced reactivity to vaccine antisera
Antigenic characterisation using haemagglutination inhibition (HAI) and ferret antisera showed a tendency toward reduced reactivity of K viruses to antisera raised against the NH vaccine strains; a WHO meeting and early lab reports signalled “low reactivity” and “mismatch” in vitro [2] [3]. England’s national dataset found reduced HAI titres over time consistent with genetic diversification and only a subset of K viruses were recognised within fourfold of homologous titres against certain vaccine‑like antisera [2].
3. Epidemiology: K spread rapidly after vaccine strain selection
Subclade K was first detected late in the SH 2025 season — after vaccine strain selection — and by mid‑late 2025 had been deposited from many countries and accounted for a large fraction of global H3N2 sequences in GISAID in May–November 2025 (roughly a third of H3N2 sequences over that window, with higher proportions in some EU/EEA reports) [3] [4]. National reports from England and countries including Canada and Japan documented early dominance of K in their 2025–26 seasons [2] [5] [6].
4. Vaccine effectiveness: lab mismatch does not equal no protection
Surveillance groups and public health agencies caution that antigenic differences measured in vitro do not automatically translate into zero protection. ECDC and other bodies note limited real‑world VE data early in the season and emphasize that vaccines often still reduce severe outcomes despite antigenic differences observed in vitro [3]. England’s early characterisation emphasised uncertainty about how VE against clinical disease will be affected and presented antigenic lab findings alongside an admitted lack of mature VE estimates [2] [3].
5. How the selection timeline amplified the problem
WHO’s vaccine strain recommendations for NH 2025–26 were based on viruses circulating before K emerged; subclade K’s rise occurred after manufacturers had been told the target strains, producing a timing mismatch (K emerged late in SH 2025 after J/J.2 had been selected) [7] [5]. Multiple outlets and analyses explicitly link that calendar to why K is antigenically divergent from the vaccine strain used in 2025–26 vaccines [5] [8].
6. Competing signals and caveats in the record
Not all data are uniform: some antigenic assays show partial recognition of K by certain post‑infection antisera (for example ferret antisera against an England isolate reacted moderately well to a subset of K viruses) and early clinical signals in some locales suggest vaccines still confer protection against severe disease in some age groups [2] [3]. At the same time, multiple independent public health reports characterize the divergence as “significant” and point to a substantial proportion of antigenically distinct H3N2 viruses [3] [1].
7. What this means for the public and for surveillance
The evidence supports that meaningful antigenic change has occurred in circulating H3N2 (subclade K) relative to the vaccine strain, documented genetically and in vitro [1] [2] [3]. Public health agencies stress continued vaccination because even imperfectly matched vaccines can lower hospitalizations and deaths, and they call for intensified genetic, antigenic and VE monitoring to quantify real‑world impact as the season progresses [3] [2].
Limitations: available sources do not mention late 2025–2026 finalized, large-scale VE estimates covering the whole season; early studies and preprints dominate some assertions and ongoing surveillance will refine the picture [2] [3].