Repeated Annual Influenza Vaccination in Older Adults Induces Comparable Seroprotection Despite Reduced Antibody Fold Rise: A 6-Month Prospective Cohort Study in China

Background: Annual influenza vaccination is a WHO-recommended strategy for preventing seasonal influenza and its associated severe complications in older adults. Nevertheless, influenza vaccine effectiveness is often reduced in the elderly population and there remains an ongoing debate regarding whether repeated vaccination attenuates immune response. Methods: We conducted a prospective observational study to estimate the trivalent inactivated influenza vaccine-induced antibodies in older adults vaccinated for two consecutive years (2022–2023 and 2023–2024) and those with vaccines administered in a single season (2023–2024). Serum samples were collected concurrently with vaccination and at 30 and 90/180 days post-vaccination for hemagglutination inhibition (HAI) tests. Results: The participants administered two consecutive vaccinations had markedly higher pre-vaccination geometric mean titers (GMTs) and seroprotection rates for influenza A/H1N1 and A/H3N2. However, no intergroup differences were observed for H1N1, H3N2 or B/Victoria strains at 30, 90, or 180 days post-vaccination. At 30 days post-vaccination, participants with two consecutive influenza vaccinations showed significantly lower fold rises against the three strains and seroconversion rates (SCRs) for H1N1 and H3N2. The results of the subgroup analyses were largely consistent with the primary findings, with the exception of the A/H1N1 strain among individuals with pre-vaccination titers <1:10 at day 30. Conclusions: Immune responses vary by antigen type, and the influenza vaccine induces comparable serological response in the elderly, irrespective of their prior vaccination history.