How effective is the 2025–26 flu vaccine against H3N2 subclade K in real-world studies?
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Executive summary
Early real-world studies from the United Kingdom and pooled European surveillance indicate that the 2025–26 seasonal influenza vaccine retains meaningful protection against the emergent H3N2 subclade K: roughly 72–75% effectiveness against emergency-department attendance and hospital admission in children and adolescents, and about 32–39% effectiveness in adults in early UK analyses [1][2][3]. Laboratory antigenic testing, however, documents reduced reactivity of subclade K viruses with antisera raised to the 2025–26 vaccine strains, so these real-world estimates are preliminary and subject to change as the season progresses [4][5].
1. What the early real-world studies actually measured and reported
The clearest real-world signal comes from UK Health Security Agency analyses reported in preprints and summarized by multiple outlets showing vaccine effectiveness (VE) against influenza-related emergency-department visits and hospital admission of roughly 70–75% in children aged 2–17 and about 30–40% in adults during the early 2025–26 season when subclade K dominated circulation [1][6][2][3]. European Centre for Disease Prevention and Control (ECDC) surveillance and a multi-country test-negative study included hundreds of cases and controls to generate early VE estimates but emphasized that data remain limited and temporally concentrated in the autumn period [7][5].
2. Why laboratory antigenic data paint a more cautious picture
Antigenic characterization using haemagglutination inhibition and ferret antisera shows reduced reactivity of many J.2.4/J.2.4.1 (subclade K) viruses to the 2025–26 northern-hemisphere vaccine reference strains, indicating antigenic drift driven by mutations such as T135K and K189R among others—findings that raised WHO concern during vaccine composition deliberations [4]. That laboratory signal raises the possibility of reduced protection against infection or mild disease even while protection against severe outcomes may persist [4][5].
3. Why VE against severe outcomes can remain higher despite antigenic drift
Multiple public-health commentaries and surveillance summaries point out that antibody tests capture only one arm of immunity; population-level VE against severe disease often remains stronger than lab-predicted neutralization because of cross-reactive immune responses and cellular immunity, and early UK data suggest retained high protection against hospital-level illness in children and moderate protection in adults [6][8][9]. Historical comparisons from prior H3N2 seasons show vaccine effectiveness against hospitalization in the 50–60% range in some years, and several observers note the current figures fall within typical seasonal variation [10][11].
4. Important limits, uncertainties and competing narratives
Surveillance coverage is incomplete, and several public documents caution that real-world VE data are preliminary: the ECDC explicitly notes limited VE data for 2025–26 and the UK interim VE report carries caveats about timing and sample sizes [5][12]. Media framing has oscillated between alarmist “superflu” headlines and reassurances that vaccines still prevent serious illness, reflecting differing editorial incentives and the political salience of early-season surges; both narratives are grounded in parts of the evidence but neither captures the full uncertainty [11][13]. Geographic variation in subclade K prevalence also means VE estimates from the UK or Europe may not generalize to places where K is less common or where different age cohorts are affected [14][8].
5. What this means for population risk and policy now
Taken together, early real-world studies suggest that the 2025–26 vaccine provides substantial protection against severe outcomes from H3N2 subclade K in children and modest protection in adults, even as laboratory assays document antigenic mismatch that could blunt protection against infection and mild disease [1][4][2]. Public-health agencies and analysts therefore emphasize vaccination to reduce hospital burden and recommend ongoing surveillance and linked clinical VE studies to update estimates as more data accrue; the current evidence is encouraging on severe-disease prevention but incomplete on durability and performance across all age groups and settings [5][9].