Effectiveness of seasonal influenza vaccine against dominant A(H1N1)pdm09 in adults ≥ 60 years: a multicenter test-negative design in Zhejiang, China, 2024–2025

Zhejiang Province, China, has implemented a free influenza vaccination program for the elderly population for five consecutive years. However, data on real-world vaccine effectiveness against influenza among the local elderly population during the 2024–2025 influenza season are still lacking. A multicenter, retrospective test-negative design (TND) was adopted in this study. Sentinel surveillance networks were established across designated sentinel hospitals in six cities of Zhejiang Province, covering the period from October 2024 to July 2025. On a weekly basis, all or a systematic sample of patients aged ≥ 60 years presenting with influenza-like illness (ILI) were enrolled in the study. Epidemiological data were collected, respiratory specimens were obtained, and laboratory assays were conducted to detect influenza virus types and subtypes. Of the 4694 enrolled elderly patients with ILI, 1587 (33.81%) were influenza-positive, with A(H1N1)pdm09 being the dominant subtype (93.3%). Vaccination coverage was 32.72% (1536/4694). After adjusting for age, sex, chronic comorbidities, calendar week, and city, the overall VE was 53.3% (95% CI: 45.4–60.2). VE estimates by age group were 56.9% (95% CI: 45.8–65.8) for individuals aged 60–69 years, 51.2% (95% CI: 36.2–62.8) for 70–79 years, and 57.7% (95% CI: 37.2–71.8) for those aged ≥ 80 years. When compared with non-consecutive vaccination in the current season, VE for two, three, and four consecutive seasons was 44.6% (95% CI: 31.1–55.5), 35.5% (95% CI: 17.5–49.7), and 38.6% (95% CI: 18.8–53.6), respectively. Protection waned from 58.0% (95% CI: 37.6–71.7) within 59 days post-vaccination to 42.8% (95% CI: 33.4–50.9) between 60 and 180 days. Furthermore, vaccination provided effective protection against moderate-to-severe influenza (68.8%, 95% CI: 50.0-80.6) and influenza-associated hospitalization (53.9%, 95% CI: 37.3–66.0). In the 2024–2025 season in Zhejiang, influenza vaccination offered moderate protection against laboratory-confirmed influenza among adults aged ≥ 60 years. While VE waned over time, consecutive vaccination maintained moderate effectiveness. The vaccine also provided substantial protection against moderate-to-severe influenza and hospitalization.