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Which influenza A(H3N2) clade was included in the WHO 2025 vaccine recommendation?

Checked on November 9, 2025
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Executive Summary

The WHO’s 2025 vaccine recommendation for influenza A(H3N2) specified two different H3N2-like components depending on vaccine production platform: A/Croatia/10136RV/2023-like virus for egg-based vaccines and A/District of Columbia/27/2023-like virus for cell culture, recombinant protein, or nucleic acid vaccines. This dual recommendation was reflected in public health communications in late February–March 2025 and echoed in U.S. regulatory guidance for the 2025–2026 season, signaling a deliberate platform-specific choice to optimize antigenic match and vaccine effectiveness across manufacturing methods [1] [2] [3].

1. Why WHO picked two different H3N2 picks — a technical fix with broad implications

On 28 February 2025 the WHO’s advisory recommendation announced a split H3N2 composition: A/Croatia/10136RV/2023-like for egg-based vaccines and A/District of Columbia/27/2023-like for cell/recombinant/nucleic acid vaccines, reflecting observed antigenic differences arising during egg adaptation and laboratory propagation. Vaccine strain selection commonly differentiates egg- and non-egg-derived antigens because influenza viruses can acquire egg-adaptive mutations that change antigenicity and reduce effectiveness; by recommending a cell- or recombinant-matched strain for those platforms, the WHO aimed to preserve antigenic fidelity for non-egg vaccines while accommodating the realities of egg-based production capacity [1] [3]. Public health agencies and manufacturers welcomed the clarity because platform-specific guidance can improve the expected match between circulating H3N2 viruses and vaccine-induced immunity, though it complicates procurement and messaging.

2. U.S. regulators followed with aligned guidance — coordination between WHO and FDA

The U.S. Food and Drug Administration published aligned recommendations in March 2025 endorsing the same platform-specific H3N2 components: A/Croatia/10136RV/2023-like for egg-based formulations and A/District of Columbia/27/2023-like for cell- or recombinant-based vaccines for the 2025–2026 U.S. influenza season. This synchronization between WHO (Feb 2025) and FDA (Mar 2025) was intended to harmonize vaccine composition across global and national supply chains, enabling manufacturers to finalize seed strains and production plans. Alignment reduces the risk of divergent vaccine antigens complicating international distribution, yet it also means that seasonal vaccine effectiveness will depend on both how well these selected strains represent circulating H3N2 clades and on production-specific antigenic fidelity [2].

3. Independent reporting and public health assessments — consensus and caveats

Reporting outlets and interim effectiveness studies in 2025 noted the H3N2 swap and the platform split, describing the move as a response to evolving H3N2 clades and laboratory evidence of differential antigenic behavior in egg propagation. Independent analyses emphasized that while the selection of A/Croatia/10136RV/2023-like and A/District of Columbia/27/2023-like strains represents a scientifically grounded effort to maximize match, vaccine performance will still hinge on how H3N2 viruses evolve during circulation and on real-world effectiveness data collected post-deployment [4] [5]. Observers flagged that interim data from the Southern Hemisphere 2025 rollout and early Northern Hemisphere surveillance would be crucial for validating the choice and informing future recommendations.

4. What this means for policy, manufacturers, and clinicians — tradeoffs and operational realities

The dual-component choice imposes operational tradeoffs: manufacturers using eggs received a strain optimized for their processes, while cell and recombinant producers received a different H3N2 antigen designed to avoid egg-adaptive changes; this reduces the antigenic compromise inherent to one-size-fits-all selections but increases supply-chain complexity. Health authorities must communicate these nuances to clinicians and the public to manage expectations about comparative vaccine effectiveness across platforms. Procurement planners must also reconcile platform-specific stockpiles with national needs, and clinicians should be prepared to interpret post-vaccination surveillance data that may show platform-specific performance differences [1] [2].

5. Bottom line and where to watch next — evidence will arrive with surveillance

The clear factual answer is that the WHO’s 2025 recommendation named A/Croatia/10136RV/2023-like for egg-based vaccines and A/District of Columbia/27/2023-like for cell/recombinant/nucleic acid vaccines, a platform-differentiated H3N2 strategy announced in February–March 2025 and adopted in subsequent national guidance [1] [2] [3]. The key open question is empirical: will real-world effectiveness data from the 2025–2026 seasons validate the platform-specific strategy? Watch post-season surveillance reports and vaccine effectiveness studies from Southern and Northern Hemisphere deployments for definitive performance evidence [5] [4].

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