Prior infection with influenza virus but not vaccination leaves a long-term immunological imprint that intensifies the protective efficacy of antigenically drifted vaccine strains.

•Prior influenza infection, but not immunization, intensified the vaccine efficacy of a drift strain.•Antigenic distances between infecting vs. immunization strains were not a limiting factor for heightened vaccine efficacy.•Prior infection broadened cross-reactivity of vaccine strains against antigenically further drifted strains.•The impact of prior infection for enhancing vaccine efficacy was long-lasting.