How did egg-based versus cell- or recombinant H3N2 vaccines perform in 2025-2026?
Executive summary
Real‑world UK data show the 2025–26 seasonal vaccine—designed with different H3N2 strains for egg‑based and for cell/recombinant products—still provided substantial protection against severe outcomes despite antigenic drift: vaccine effectiveness (VE) against emergency department attendance and hospital admission was about 72–75% in children and adolescents and 32–39% in adults in England [1] [2]. Regulatory bodies intentionally recommended different H3N2 components for egg‑based versus cell/recombinant vaccines for 2025–26 because the viruses used in manufacturing and egg‑adaptation change antigenicity [3] [4] [5].
1. Why two different H3N2 formulations this year — manufacturing realities, not marketing spin
Vaccine strain selection for 2025–26 deliberately split the H3N2 component by production method: egg‑based vaccines were recommended to include an A/Croatia/10136RV/2023 (H3N2)‑like virus, while cell‑ or recombinant‑based vaccines were recommended to include an A/District of Columbia/27/2023 (H3N2)‑like virus [4] [5]. Federal and WHO advisers make separate picks because egg‑propagation can introduce adaptive changes in HA (haemagglutinin) that affect antigenicity; regulators therefore choose reference viruses appropriate to each manufacturing platform rather than imply inherent superiority of one platform [3] [4].
2. Antigenic drift: subclade K and a measurable mismatch in the lab
A new H3N2 subclade K (J.2.4.1) expanded rapidly and showed reduced reactivity to antisera raised against the planned 2025–26 vaccine strains in laboratory assays and ferret sera, indicating antigenic drift from the vaccine reference strains [6] [2] [7]. European and WHO serology reports documented lower antibody titres against many recently circulating H3N2 variants compared with the vaccine reference viruses, supporting the laboratory signal of a mismatch [8] [7].
3. But clinical protection held up — especially in children
Despite reduced ferret antisera recognition, early real‑world effectiveness estimates from England found vaccines kept protecting against clinical severity: VE against emergency department attendance and hospital admission was 72–75% in children and adolescents (<18) and 32–39% in adults during autumn 2025 [1] [2]. UKHSA emphasised that these levels are within typical ranges and that vaccination remains an effective preventive tool even in the presence of drifted H3N2 viruses [9] [1].
4. Why adults — particularly older adults — saw lower VE
Multiple sources note that H3N2‑dominant seasons historically produce lower VE and worse outcomes in older adults, and preliminary VE here was lower in adults than in children [10] [2]. Immunosenescence, prior vaccination history and antigenic drift can all blunt antibody responses in adults; studies of enhanced vaccines (high‑dose, adjuvanted, recombinant HA) are meant to address that but prior vaccination effects can persist [11].
5. Cell/recombinant vs egg‑based: lab advantages vs real‑world evidence
Cell and recombinant products use non‑egg propagation and may avoid egg‑adaptation changes that can alter HA antigenicity; that mechanistic advantage underlies different strain choices and published immunology showing recombinant HA can elicit broader responses in some settings [5] [12]. However, available real‑world VE estimates cited here come from mixed national surveillance (England) and report overall clinical effectiveness by age groups rather than by specific manufacturing platform, so direct comparative effectiveness between egg‑based and cell/recombinant vaccines in 2025–26 is not quantified in these sources [1] [2] [7]. Available sources do not mention head‑to‑head national VE estimates broken down by vaccine manufacture type for 2025–26.
6. What experts say about public health choices this season
Health agencies emphasised continued vaccination because even partially matched vaccines reduce hospitalisations and deaths; UKHSA and other commentators urged vaccination alongside surveillance and hygiene measures as subclade K spread [9] [13] [7]. The ECDC and WHO stressed the need for robust real‑world studies as the season evolves to quantify any decline in protection [7] [14].
7. Limits of the current evidence and what to watch next
Current VE estimates are early, derived from England’s autumn surveillance and antigenic lab assays; they reflect ED/hospital outcomes and may not capture outpatient illness or long‑term season performance [1] [2]. Wider, stratified VE analyses (by age, comorbidity, and by egg vs cell/recombinant product) are still pending in the sources provided; available sources do not mention those breakdowns. Future reports from national IV‑NETworks and WHO updates will determine whether the early maintenance of protection endures as circulation changes [10] [7].
Bottom line: laboratory data show antigenic drift by H3N2 subclade K and regulators deliberately set different H3N2 strains for egg versus cell/recombinant vaccines [4] [2]. Nevertheless, early real‑world surveillance from England found vaccines continued to prevent a substantial proportion of severe presentations — especially in children — supporting public‑health advice to vaccinate even in a partially mismatched season [1] [9].