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Background: Immune responses to influenza vaccination can be weaker in older adults than in other age groups. We hypothesized that antibody responses would be particularly weak among repeat vaccinees when the current and prior season vaccine components are the same.Methods: An observational study was conducted among 827 older adults (aged ≥75 years) in Hong Kong. Serum samples were collected immediately before and 1 month after receipt of the 2015-2016 quadrivalent inactivated influenza vaccine. We measured antibody titers with the hemagglutination inhibition assay and compared the mean fold rise from prevaccination to postvaccination titers and the proportions with postvaccination titers ≥40 or ≥160.Results: Participants who reported receipt of vaccination during either of the previous 2 years had a lower mean fold rise against all strains than with those who did not. Mean fold rises for A(H3N2) and B/Yamagata were particularly weak after repeated vaccination with the same vaccine strain, but we did not generally find significant differences in the proportions of participants with postvaccination titers ≥40 and ≥160.Conclusions: Overall, we found that reduced antibody responses in repeat vaccinees were particularly reduced among older adults who had received vaccination against the same strains in preceding years. [ABSTRACT FROM AUTHOR]