Influenza strain-specific T cell responses longitudinally post-vaccination with FluZone

Despite seasonal vaccination strategies, influenza viruses still cause significant morbidity and mortality. While vaccine efficacy is generally high, effectiveness varies from year-to-year and can be impacted by numerous host factors, including age, sex, obesity, and immune history. Therefore, understanding host immune factors that promote robust vaccine responses and protection from influenza infection and disease, is important for improving vaccine design and evaluation. This study focuses on influenza-specific T cells, an understudied component of influenza vaccination responses and long-term protection from infection. This study measured influenza strain-specific T cell responses in 40 participants longitudinally following immunization with the inactivated, quadrivalent FluZone vaccine. Influenza-specific T cells were restimulated using live virus representing the four strains included in the FluZone construct. Strain-specific T cell responses were correlated with plasma chemokine and cytokine levels, and humoral immunity, quantified by hemagglutination inhibition assay. Activated and degranulating T cells were frequently detected against all strains longitudinally post-vaccination and positively correlated with serological responses. Cytokine-producing T cells were less frequently detected, and they peaked early post-vaccination, concurrent with elevated plasma IFNγ and CCL4. Changes in strain-specific T cells post-vaccination and correlation with serological responses was stronger for influenza A subtypes than B subtypes. Dynamics of cytokine-producing T cells early post-influenza vaccination may reflect ongoing immune responses, but activated and degranulating T cells better represent longitudinal changes in serological responses. Differences between T cells specific to influenza A and B subtypes warrant further investigation to understand why they diverge and the relevance to vaccine design and evaluation.