Impaired IL-17 and cytotolytic responses to influenza vaccine antigens in aging nonhuman primates

Abstract

Abstract Despite widespread flu vaccination, influenza remains a major cause of morbidity and mortality in the elderly. The early immune response, including CD4+ helper T cells, and CD8+ CTLs, plays a critical role in efficient control of virus and initiation of adaptive immunity. However, the correlates of protection in the elderly are not well understood. Here, we sought to investigate early cellular responses to re-exposure with seasonal flu vaccine antigens in a cohort of pre-vaccinated young and old rhesus macaques (human age equivalent of 30–45 yrs, and 55–85 yrs). In vitro T cell responses were examined following overnight stimulation of PBMCs with flu vaccine antigens by flow cytometry for Th1-type and Th17-type cytokine responses, and cytolytic functions. Notably, older macaques showed significantly impaired IL-17 production and CD107a upregulation in response to vaccine antigens, along with greater HLA-DR +/PD-1 +CD8 T cells. Further, they produced significantly higher TNF-α than young macaques. These results suggest that circulating flu vaccine-specific T cells in older macaques are deficient in mucosal barrier-protective and cytotolytic functions and possess a dominant proinflammatory function. These findings suggest that re-exposure to flu vaccine antigens in older individuals likely induces a proinflammatory response that is impaired in cytolytic capacity and the ability to repair lung mucosal damage during influenza infection, thereby resulting in more severe disease outcomes. Further studies on in vivo modulation of proinflammatory T cells while enhancing IL-17 functions during vaccination could support the development of more effective influenza vaccine strategies for older adults.