What are the reported efficacy estimates against predominant 2025-2026 influenza strains in randomized trials?
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Executive summary
Randomized trial data for 2025–2026 influenza vaccines are limited in the available reporting; most contemporary efficacy/effectiveness figures come from observational VE networks and Southern Hemisphere surveillance rather than large randomized trials (not found in current reporting). Interim observational estimates: U.S. VE networks reported outpatient VE in adults at roughly 36% to 55% and hospitalization VE at about 41% to 55% during the 2024–25 season [1]. Southern Hemisphere interim analyses for the 2025 vaccines—whose composition matches the 2025–26 Northern Hemisphere vaccine—show ~50% reduction in outpatient visits and hospitalizations [2].
1. What randomized trials actually report — the evidence gap
Randomized, placebo‑controlled phase 3 trial results specifically reporting efficacy against the predominant 2025–2026 circulating strains are not present in the supplied documents; the main randomized vaccine trial cited in the sources is a modRNA influenza vaccine study reporting design and endpoints, not mid‑season efficacy against 2025–26 strains [3]. Available sources do not mention completed randomized trials that yield head‑to‑head efficacy estimates for the 2025–2026 season; instead, public health agencies and surveillance networks have published observational VE and interim surveillance analyses [1] [2].
2. Observational VE numbers you’ll see cited — outpatient and hospitalization protection
U.S. interim VE networks for the 2024–25 season reported adult outpatient VE estimates of roughly 36% and 54% from two networks, and hospitalization VE estimates of about 41% and 55% from two networks; the CDC interpreted these as evidence that the 2024–25 vaccine reduced medically attended influenza and hospitalizations [1]. For the 2025 Southern Hemisphere season (vaccine composition shared with 2025–26 Northern Hemisphere), pooled interim estimates found vaccination reduced outpatient visits by 50.4% and hospitalizations by 49.7% [2].
3. How observational VE differs from randomized efficacy and why that matters
Observational VE estimates (test‑negative designs, surveillance networks) control for some confounders and measure real‑world protection but are not randomized efficacy trials; they can vary by study network, outcome (outpatient illness vs. hospitalization), age group, and circulating strain mix [1]. Sources note VE ranges vary year to year—typical seasonal VE historically runs from roughly 30% to 60%—so single network estimates are context‑dependent and should not be conflated with randomized trial efficacy [4] [5].
4. Age and outcome matter — children versus adults and severe disease
Several reports show protection is stronger for some outcomes and age groups: CDC interim data for 2024–25 showed VE estimates among children and adolescents in outpatient settings of 32%–60% and higher hospitalization protection in some pediatric estimates [1]. Later analyses from the UK (preprint cited in reporting) and pooled Southern Hemisphere data suggest 2025 vaccines may protect children against hospital attendance at higher levels (e.g., reported 70%–75% in one preprint for children) while adult protection can be lower (around 30%–40%) [6] [2].
5. Strain match and seasonality drive observed protection
Public health sources emphasize that VE depends on the match between vaccine strains and circulating viruses; the FDA’s composition decisions for 2025–26 used surveillance data and mid‑season VE inputs, and the 2025 Southern Hemisphere composition equals the 2025–26 Northern composition—hence Southern Hemisphere VE can be a useful early signal [7] [2]. Reports also warn that emergent H3N2 subclades (e.g., “subclade K”) can reduce vaccine match and shift adult VE downward while still preserving protection against severe disease in many settings [6] [8].
6. Conflicting single‑site findings and interpretation risks
A large Cleveland Clinic employee cohort study concluded they “were unable to find that the influenza vaccine has been effective in preventing infection” during 2024–25 and reported a negative VE estimate within that cohort; that single‑institution observational finding contrasts with multi‑network CDC estimates showing measurable VE and underscores heterogeneity across studies and populations [9] [10] [1]. Readers should note single‑site analyses can reflect local testing, exposure, and behavioral patterns and do not replace multi‑center surveillance networks [1] [9].
7. Bottom line and what the sources recommend
Randomized trial efficacy numbers for vaccine performance specifically against predominant 2025–2026 strains are not documented in the provided material; instead, the consistent message from CDC, MMWR, and pooled Southern Hemisphere surveillance is that the 2024–25 and 2025 vaccine compositions have shown moderate protection—roughly 36%–55% in some U.S. networks and about 50% in Southern Hemisphere pooled data—particularly for preventing healthcare‑attended illness and hospitalization [1] [2]. Public health agencies continue to recommend vaccination because even partial VE reduces hospitalizations and severe outcomes [1] [2].