Longitudinal analysis of IAV-specific CD8⁺ T cell response to the high dose influenza vaccine (Fluzone) in healthy older adults

Influenza infection remains a leading cause of death among older adults worldwide. While vaccines offer an effective means of reducing the severity of influenza, their efficacy reduces in this demographic. To gain insight into the adaptive immune response, we conducted an analysis of antigen-specific CD8⁺ T cells before and after the administration of the high-dose seasonal influenza vaccine (Fluzone) over six seasons (2014, 2018, 2019, 2021, 2022, and 2023) in a cohort of healthy older adults (n=37, M=18, F=19, aged 72-92, spanning visits 1-3). Using the HAI assay, we observed seroconversion (a 4-fold antibody increase post-vaccination) for most strains (>67% of strains) in 46% of donors, for less than half of the strains (25-50% of strains) in 13% of donors, and no seroconversion (0% of strains) occurred in 30% of donors. Notably, there was a twofold higher occurrence of seroconversion for Influenza A virus (IAV) (51%) compared to Influenza B virus (IBV) (25%). As age advanced, 54% of donors exhibited a reduced antibody response, while 23% either experienced no change or saw an increase in their antibody response. Presently, we investigate the frequency and clonotype of influenza A virus (IAV) M1_158-166-specific CD8⁺ T cells, tracking their changes post-vaccination and over a span of 1-5 years. This endeavor aims to uncover new insights into the molecular basis of the reduced antigen-specific CD8⁺ T cell response observed in certain older adults.