Effects of repeated influenza vaccination and infection on durable seroprotection in healthcare workers

Rapid evolution of seasonal influenza viruses necessitates annual vaccine reformulation to match circulating strains. Healthcare workers (HCWs) and high-risk groups are prioritised for annual influenza vaccination. However, repeated annual vaccination may affect immune protection. This study investigated the hemaglutination-inhibition (HI) antibody responses following influenza infection or repeated seasonal vaccination over four seasons in 250 HCWs with well-defined vaccination histories. Unvaccinated HCWs had high infection rates, with pre-existing antibodies providing protection. Infection or hybrid immunity generated higher antibody responses to A/H3N2 viruses than vaccination alone, whereas vaccination induced more durable A/H1N1 and B virus-specific antibodies. Vaccination boosted seroprotective antibodies, irrespective of previous vaccination histories. Moreover, repeated vaccination with the same virus for more than three consecutive seasons blunted antibody responses, while updating vaccine strains improved immunity. Annual influenza vaccination of HCWs should be strengthened to increase uptake, but next-generation influenza vaccines must improve vaccine immunogenicity, particularly against A/H3N2 viruses.