Relative vaccine efficacy vs. H3N2 with Flu Vaccine
Executive summary
Early data show this season’s flu vaccines still cut severe outcomes but provide reduced protection against H3N2 compared with other strains: UK real‑world estimates put vaccine effectiveness (VE) at 70–75% to prevent hospital attendance in children and 30–40% in adults against the 2025/26 vaccine when H3N2 subclade K dominated [1] [2]. Southern Hemisphere surveillance found overall VE ≈50% against medical visits/hospitalization but only ~37% against H3N2 [3]. A new modRNA influenza vaccine showed 34.5% relative efficacy versus a control for influenza‑like illness in a clinical trial where A/H3N2 was one cause [4].
1. Why H3N2 matters this season — the virus and the mismatch
H3N2 is historically the worst offender for vaccine performance and severe outcomes in older adults, and the emergence of a genetically distinct subclade K (J.2.4.1) after vaccine strain selection raised alarms because laboratory antigenic testing showed reduced reactivity with ferret antisera to the vaccine reference strain [5] [6]. Public health teams explicitly note that it is “unclear how 2025/26 vaccine effectiveness (VE) against clinical disease may be affected” by these mutations [6].
2. What real‑world studies are showing now
Multiple early, independent data streams point to meaningful but lower protection against H3N2. The UK Health Security Agency reported VE of 70–75% to prevent hospital attendance in children and 30–40% in adults despite subclade K circulation [1] [2]. Southern Hemisphere multicountry analyses—used as a preview for the Northern Hemisphere—estimated adjusted VE ~49.7% against any influenza‑associated hospitalization and specifically about 37.2% against H3N2 [3].
3. How to interpret those percentages in practical terms
A VE of ~30–40% in adults against hospital attendance means vaccinated adults had roughly one‑third lower odds of the measured severe outcome compared with unvaccinated adults in the studied populations; for children, current estimates are substantially higher [1]. The Southern Hemisphere aggregate result—about half reduction in medical care and hospitalization overall—shows vaccines still blunt disease burden even when H3N2 performance lags [3].
4. New vaccine platforms and head‑to‑head clinical data
A randomized trial of a modified mRNA (modRNA) influenza vaccine met superiority vs a control for influenza‑like illness with a relative efficacy of 34.5% (95% CI, 7.4–53.9) in the trial population; A/H3N2 and A/H1N1 contributed cases to that outcome [4]. That signals new platforms can show improved endpoints in trials, but clinical trial populations and circulating strains differ from real‑world, season‑long effectiveness measures [4].
5. Conflicting signals and study limitations to bear in mind
Sources present mixed but not contradictory pictures. UK and Southern Hemisphere field VE studies show protection varies by age and outcome (clinic visit vs hospitalization) and that H3N2 VE is lower than for H1N1 or B [1] [2] [3]. Lab antigenic assays suggest reduced match for subclade K but cannot alone quantify population VE [6]. Available sources do not mention long‑term durability of protection across the whole season nor exhaustive age‑stratified VE for all settings beyond those reports (not found in current reporting).
6. What experts and agencies are advising now
Public health authorities continue to recommend vaccination for everyone ≥6 months because vaccines reduce hospitalizations and deaths even in mismatch years; multiple sources explicitly state vaccination “remains an effective preventative tool” and that shots reduce severe disease [1] [3]. Commentators and agencies emphasize enhanced‑dose vaccines for older adults often yield better protection against hospitalization in H3N2‑dominant seasons [7].
7. Bottom line for clinicians, institutions and the public
Expect reduced but meaningful protection against H3N2 this season: real‑world VE against H3N2 has been reported around the high‑30s percent for hospitalization [3], while UK early data show children retain strong protection (70–75%) and adults modest protection (30–40%) against hospital attendance [1] [2]. Given that vaccination still lowers severe outcomes and new vaccine platforms have promising trial results, public health guidance remains uniform: vaccinate, prioritize enhanced doses for older adults, and maintain surveillance to detect how VE evolves as the season progresses [4] [1] [3].
Limitations: these conclusions are drawn from early-season and regional analyses cited above; antigenic assays and clinical VE estimates can diverge as circulation changes, and the sources explicitly note uncertainty about how subclade K will affect clinical VE over the full season [6].