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How effective is the 2025-2026 influenza vaccine against H3N2 variants?
Executive Summary
The 2025–2026 influenza vaccine contains an updated A(H3N2) component and is expected to provide moderate protection—roughly around 40–50% on average—against circulating H3N2 viruses, with somewhat higher protection against hospitalization in children in some interim analyses and lower protection reported in some adult outpatient studies [1] [2] [3]. Multiple expert reviews caution that H3N2 has historically produced the weakest vaccine effectiveness (VE) among seasonal strains because of rapid antigenic drift and production-related changes, meaning real-world VE will vary by age, vaccine formulation (egg-based vs. cell/recombinant, standard vs. high-dose/adjuvanted), and the exact match between vaccine strains and circulating variants [4] [5].
1. Why H3N2 Keeps Tripping Up Vaccines—and What That Means Now
H3N2 viruses evolve rapidly, and vaccine effectiveness has repeatedly lagged behind other influenza types; this historical pattern explains why experts expect only modest VE for the 2025–2026 H3N2 component despite updating the strain to an A/Croatia/10136RV/2023-like or related virus in some formulations [4] [6]. Scientific analyses show two recurring mechanisms that reduce VE: antigenic drift in circulating H3N2 lineages and egg-adaptive mutations introduced during traditional vaccine production that alter the haemagglutinin protein targeted by immune responses; both processes can create a measurable mismatch between vaccine and circulating viruses, lowering protection particularly for outpatient illness [4] [5]. Given those mechanisms, expect variability across populations and vaccine types rather than a single uniform effectiveness number.
2. What the Southern Hemisphere and Interim Data Suggest About Real-World Performance
Interim observational analyses from the Southern Hemisphere and early-season reports point toward roughly 30–50% reductions in medically attended influenza and some higher reductions in severe outcomes among children and vaccinated high-risk adults, with one study reporting an adjusted VE of about 37% against H3N2 in severe acute respiratory infection patients and pooled estimates near 48% for adults 18–64 against hospitalization in broader meta-analyses [1] [3] [2]. These real-world numbers align with expectations from vaccine-strain match assessments: when the vaccine strain is reasonably well matched, VE often reaches the 40–60% range for preventing outpatient illness; when drift or production changes degrade antigenic similarity, effectiveness can fall to the lower end of prior ranges [2] [4]. This pattern underscores that early-season VE estimates are provisional and can shift as more data accumulate.
3. Formulation Matters: Egg-based vs. Cell/Recombinant and the Role of Adjuvants
Vaccine formulation choice affects H3N2 protection: cell-based or recombinant vaccines generally avoid egg-adaptive mutations and can provide better antigenic fidelity to the chosen H3N2 strain, while high-dose or adjuvanted formulations (e.g., MF59) can boost immune responses in older adults and may partially offset lower antigenic match [6] [4]. Regulatory recommendations for the 2025–2026 composition specified different H3N2 seed strains depending on platform, signaling an effort to improve match where possible, but not all manufacturers or immunization programs use the same platforms, producing heterogeneity in population-level VE [6] [7]. Public-health messaging should therefore differentiate vaccine types for older or high-risk individuals who may benefit from high-dose or adjuvanted products.
4. Age, Outcome, and Context: Who Gets Better Protection?
Effectiveness estimates vary by age and outcome: children and younger adults often see higher VE against hospitalization than older adults see against outpatient illness, partly because severe disease prevention can be more robust even when infection is not fully prevented. Meta-analyses and pooled datasets report higher VE for preventing severe outcomes in pediatric populations, while older adults frequently show lower VE against symptomatic infection unless they receive high-dose or adjuvanted vaccines [3] [4]. In practice, this means that even a vaccine with modest VE against infection can still substantially reduce serious illness and healthcare burden—a key rationale for continuing broad vaccination campaigns despite imperfect H3N2 performance [3] [5]. Targeted use of optimized formulations for seniors remains a priority.
5. What to Watch and How to Interpret Future Updates
Expect updated VE estimates through the season as national surveillance and test-negative design studies report results; early Southern Hemisphere figures and interim analyses provide a baseline but are not final verdicts [1] [2]. Policymakers and clinicians should monitor: [8] laboratory antigenic characterization of circulating H3N2 variants relative to the vaccine strain, [9] VE stratified by vaccine platform and age group, and [10] hospitalization and severe outcome trends. Be alert to competing messages: manufacturers and advocacy groups may emphasize improved formulations and benefits, while skeptics may highlight lower VE numbers from previous H3N2 seasons—both perspectives reflect facts but different emphases [4] [2]. The practical takeaway is that vaccination remains the best available protection against severe flu outcomes, even when H3N2 VE is only moderate.