Background: Repeated annual influenza vaccination has been associated with attenuated immune responses and reduced clinical effectiveness. Most studies of repeat vaccination immunogenicity have focused on the responses at 30 days after vaccination. As influenza did not circulate in Hong Kong for over two years during the COVID-19 pandemic, we were able to investigate vaccine responses in the absence of infections.

Methods: In this community-based cohort study in Hong Kong, we investigated the impact of repeated annual influenza vaccination on antibody titer boosting and waning rates of 8 contemporary vaccine strains over two years in 2021/22 and 2022/23, using hemagglutination inhibition assays. We estimated the impact of repeat vaccination on mean-fold rises in titer from before to after vaccination, and on post-vaccination titers. We investigated differences by vaccination history in antibody titer waning rates after day 14 post-vaccination using a power law model.

Results: We found differences in post-vaccination geometric mean and mean-fold rises in titers against several vaccine strains in repeat vaccinees in 2022/23 compared to 2021/22. However, although participants with higher vaccination uptake had significantly slower antibody waning after 2021/22 vaccination against A/Victoria/2570/2019, B/Phuket/3073/2013, and B/Austria/1359417/2019, they reached similar antibody titers at six months post-vaccination compared to participants with less frequent vaccination history.

Conclusions: Our findings suggest that repeated influenza vaccination is associated with reduced titer increase at day 14 post-vaccination, but has less impact on antibody levels at six months post-vaccination.