Association of vaccine‐specific regulatory T cells with reduced antibody response to repeated influenza vaccination

Abstract

AbstractRepeated annual influenza vaccinations have been associated with reduced vaccine‐induced antibody responses. This prospective study aimed to explore the role of vaccine antigen‐specific regulatory T (Treg) cells in antibody response to repeated annual influenza vaccination. We analyzed pre‐ and postvaccination hemagglutination inhibition (HI) titers, seroconversion rates, seroprotection rates, vaccine antigen hemagglutinin (HA)‐specific Treg cells, and conventional T (Tconv) cells. We compared these parameters between vaccinees with or without vaccine‐induced seroconversion. Our multivariate logistic regression revealed that prior vaccination was significantly associated with a decreased likelihood of achieving seroconversion for both H1N1(adjusted OR, 0.03; 95% CI, 0.01–0.13) and H3N2 (adjusted OR, 0.09; 95% CI, 0.03–0.30). Furthermore, individuals who received repeated vaccinations had significantly higher levels of pre‐existing HA‐specific Treg cells than those who did not. We also found that vaccine‐induced fold‐increases in HI titers and seroconversion were negatively correlated with pre‐existing HA‐specific Treg cells and positively correlated with the ratio of Tconv to Treg cells. Overall, our findings suggest that repeated annual influenza vaccination is associated with a lower vaccine‐induced antibody response and a higher frequency of vaccine‐specific Treg cells. However, a lower frequency of pre‐existing Treg cells correlates with a higher postvaccination antibody response.