Which influenza strains dominated the 2024-2025 season and how were they matched to the 2025 vaccine?
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Executive summary
The 2024–25 U.S. influenza season was dominated by influenza A, with A(H1N1)pdm09 and A(H3N2) circulating at roughly equal levels and the season classified as high severity; interim U.S. testing found many A(H3N2) viruses belonged to HA clade 2a.3a.1 and A(H1N1)pdm09 viruses to clade 5a.2a/5a.2a.1, strains that matched components selected for the 2024–25 vaccines [1] [2]. WHO, FDA and European regulators moved to trivalent formulations for 2024–25 (removing or deprioritizing the B/Yamagata component), with selected vaccine strains including A(H1N1)pdm09-, A(H3N2)- and B/Victoria-lineage–like viruses for northern hemisphere use [3] [4] [5].
1. Two A’s, one story: which viruses actually dominated the season
U.S. surveillance and CDC reporting show the 2024–25 season was led by influenza A viruses, with A(H1N1)pdm09 and A(H3N2) detected at approximately equal levels and public health authorities classifying the season as high severity based on outpatient visits, hospitalizations and deaths [1]. European and other interim reports described co‑circulation of A(H1N1)pdm09, A(H3N2) and B/Victoria, with some studies noting A(H1N1)pdm09 predominated in parts of Europe [4].
2. What strains were chosen for the 2024–25 vaccines—and why
WHO’s February 2024 consultation and subsequent FDA/EMA decisions led to Northern Hemisphere vaccine recommendations that targeted specific representative viruses: an A(H1N1)pdm09–like virus (e.g., A/Victoria/4897/2022 or A/Wisconsin/67/2022 for cell‑grown vaccines), an A(H3N2)–like virus (A/Thailand/8/2022 or related clade 2a.3a.1 strains), and a B/Victoria‑lineage virus for trivalent formulations; quadrivalent options could include a B/Yamagata component historically, though WHO and some regulators moved to de‑emphasize B/Yamagata for 2024–25 [3] [4] [6]. FDA’s VRBPAC recommended trivalent formulations for many U.S. products and specified strain selections by production method (egg vs. cell/recombinant) to maximize antigenic match and manufacturing feasibility [5] [7].
3. How well the vaccine strains matched circulating viruses during the season
CDC interim laboratory characterization showed that 286 A(H3N2) viruses from U.S. surveillance belonged to HA clade 2a.3a.1—the same clade that included the A(H3N2) strain chosen for the 2024–25 cell‑grown vaccine (A/Massachusetts/18/2022)—and sequenced A(H1N1)pdm09 viruses included clades containing the vaccine A/Wisconsin/67/2022 reference, indicating substantial antigenic overlap in many samples [2]. Multiple VE networks reported interim vaccine effectiveness estimates that varied by age and setting, with substantial protection against hospitalization in children and adolescents in some networks [2] [8].
4. Areas of mismatch and early warnings during the season
Media coverage and early CDC testing suggested that some circulating viruses were less well recognized by vaccine‑induced antibodies—particularly some H3N2 variants—which raised concerns of partial mismatch and may have contributed to season severity in places with heavier H3N2 activity [9]. European and multi‑country interim studies also described co‑circulation and variable vaccine effectiveness against different subtypes, underscoring geographic and temporal heterogeneity [4].
5. Policy shifts that affected vaccine composition and interpretation
Regulators adjusted guidance in 2024 to favor trivalent formulations for certain production pathways and, in some jurisdictions, to drop routine inclusion of a B/Yamagata component based on surveillance and candidate strain availability [6] [7] [5]. These production and policy choices affect which strains are present in U.S. and European vaccines and complicate direct comparisons across countries and vaccine types [5] [7].
6. What this means for individuals and public health
Available reporting emphasizes that even with imperfect strain match, vaccination reduced severe outcomes in 2024–25—interim U.S. VE analyses showed notable protection against influenza‑associated hospitalization in children and adolescents and variable outpatient effectiveness by age and subtype—so public‑health authorities continued to recommend vaccination for eligible persons [2] [8]. Public reporting also flagged that H3N2‑dominated seasons tend to drive higher severity and lower VE than other seasons, which helps explain the heightened impact in 2024–25 [9].
Limitations and competing perspectives: surveillance data vary by region and time, and while CDC sequencing showed alignment of many circulating viruses with vaccine reference strains [2], news reports highlighted pockets of reduced recognition by vaccine antibodies for some H3N2 variants and regional differences in dominance [9] [4]. Available sources do not mention detailed vaccine‑by‑manufacturer real‑world effectiveness across every age group; that level of granularity is not found in current reporting.