In Europe, annual influenza vaccination is recommended to elderly. From 2011 to 2014 and in 2015-16, we conducted a multicentre test negative case control study in hospitals of 11 European countries to measure influenza vaccine effectiveness (IVE) against laboratory confirmed hospitalised influenza among people aged ≥65years. We pooled four seasons data to measure IVE by past exposures to influenza vaccination. We swabbed patients admitted for clinical conditions related to influenza with onset of severe acute respiratory infection ≤7days before admission. Cases were patients RT-PCR positive for influenza virus and controls those negative for any influenza virus. We documented seasonal vaccination status for the current season and the two previous seasons. We recruited 5295 patients over the four seasons, including 465A(H1N1)pdm09, 642A(H3N2), 278 B case-patients and 3910 controls. Among patients unvaccinated in both previous two seasons, current seasonal IVE (pooled across seasons) was 30% (95%CI: -35 to 64), 8% (95%CI: -94 to 56) and 33% (95%CI: -43 to 68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Among patients vaccinated in both previous seasons, current seasonal IVE (pooled across seasons) was -1% (95%CI: -80 to 43), 37% (95%CI: 7-57) and 43% (95%CI: 1-68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Our results suggest that, regardless of patients' recent vaccination history, current seasonal vaccine conferred some protection to vaccinated patients against hospitalisation with influenza A(H3N2) and B. Vaccination of patients already vaccinated in both the past two seasons did not seem to be effective against A(H1N1)pdm09. To better understand the effect of repeated vaccination, engaging in large cohort studies documenting exposures to vaccine and natural infection is needed.

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