What were effectiveness estimates for egg-based vs cell-based H3N2 vaccines in 2025-2026 by age group?
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Executive summary
Mid‑season and manufacturer real‑world reports for 2025–26 indicate a modest but consistent relative advantage for cell‑culture (and other non‑egg) H3N2 vaccine products over egg‑based vaccines in most age groups, driven by documented egg‑adaptation of the egg H3N2 candidate strain; published season‑level pooled estimates across prior seasons center on single‑digit to low‑20% relative vaccine effectiveness (rVE) in favor of cell‑based products, but comprehensive, peer‑reviewed age‑stratified VE estimates for the 2025–26 season remain limited [1] [2] [3] [4].
1. What sources exist and what they measure
The available evidence for 2025–26 comprises: laboratory antigenic analyses showing reduced reactivity of some circulating H3N2 viruses with antisera raised against the 2025/26 egg‑propagated vaccine virus versus the cell‑propagated strain (England public health analyses; WHO serology work), national policy summaries that reviewed these data (CDC, JCVI), a manufacturer press release describing recent real‑world test‑negative studies, and broader systematic reviews/meta‑analyses of prior seasons comparing cell‑based quadrivalent vaccines (QIVc) to egg‑based vaccines [4] [5] [6] [2] [1] [3].
2. Children and adolescents (<18 years): signals of good protection but mixed comparative estimates
England’s early 2025 surveillance reported “high VE results” for children and adolescents, including cross‑protection against drifted H3N2 that may reflect live attenuated vaccine performance and broader immune responses; the same report noted greater antigenic reduction with antisera to the NH 2025/26 egg strain than to the cell strain, implying potential advantage for non‑egg approaches, but it did not publish a single, clear age‑stratified rVE number comparing egg vs cell for children [4]. Manufacturer real‑world analyses presented aggregated rVE for 6 months–64 years rather than a child‑only point estimate, so an exact 2025–26 child‑specific comparative VE for egg vs cell is not yet publicly available in peer‑reviewed form [2].
3. Adults 18–64 years: modest, consistent advantage for non‑egg vaccines
Regulatory and advisory bodies reviewed evidence showing that cell‑culture and recombinant vaccines avoid egg‑adaptation and that recombinant IIVr has demonstrated superiority to egg‑based IIVe in some analyses for adults under 65; pooled RWE across earlier seasons found an overall rVE of approximately 8.4% favoring QIVc over egg vaccines (with season‑to‑season variation and a peak rVE against H3N2 of ~25% in 2017–18 when egg adaptation was pronounced) — industry RWE for recent seasons has reported ~19.8% rVE for QIVc versus standard egg QIV in persons 6 months–64 years [3] [1] [2].
4. Older adults (≥65 years): guidance favors enhanced or cell options but direct 2025–26 comparisons are scarce
UK JCVI guidance explicitly prefers cell‑culture and recombinant vaccines over egg‑based vaccines for many adults under 65 and advises use of enhanced vaccines (e.g., high‑dose, adjuvanted) for those ≥65 while noting IIVc can be considered if other options are unavailable; however, clear published 2025–26 age‑specific VE comparisons (egg vs cell) for the ≥65 group were not located in the reviewed material, leaving uncertainty about the precise magnitude of any differential effectiveness in this age band [3].
5. Why antigenic data point toward a differential and what that means for observed VE
Laboratory antigenic testing from England and WHO‑linked serology panels found that several circulating H3N2 subclade K/J viruses showed markedly reduced reactivity (>32‑fold against egg‑propagated CVV vs smaller reductions to cell‑propagated CVV), a mechanistic rationale for worse performance of egg‑based H3N2 components in seasons dominated by these drifted viruses; policy statements (CDC, WHO, JCVI) used these data to justify inclusion of cell‑ or recombinant‑derived H3N2 strains in non‑egg vaccines for 2025–26 [4] [5] [6].
6. Bottom line and limitations of the evidence
The weight of laboratory, advisory, meta‑analytic, and recent RWE reporting indicates a modest advantage for cell‑based or recombinant H3N2 vaccines over egg‑based vaccines in 2025–26, most consistently observed in persons under 65 and historically most pronounced in seasons with egg‑adaptation (pooled rVE ~8% overall across prior seasons, up to ~20% reported in recent RWE for 6 months–64 years and higher in specific past seasons) — but peer‑reviewed, fully age‑stratified VE estimates specific to 2025–26 remain incomplete in the public record, and manufacturer‑sponsored RWE may carry commercial bias and uses aggregate age bands that limit fine‑grained interpretation [1] [2] [3] [4].