The impact of aging on adaptive immune responses to improved licensed influenza vaccines 4708

Abstract Description Influenza-related illness is a significant cause of morbidity and mortality in older adults. With age comes decreased antibody responses, reduced naïve thymic output, and increased T cell senescence. While recent vaccine formulations have improved the magnitude of antibody responses in older adults, this population remains at an increased risk of severe influenza-related illness. In a cohort of 15 older adults (over 65) and 32 younger adults (under 45), we investigated vaccine-elicited B and CD4+ T cell responses. At day 28 post-vaccination, both age groups mounted similar antibody responses and achieved equivalent titers for all vaccine antigens. At day 7 post-vaccination, younger adults had increased frequencies of H1N1 and H3N2 reactive OX40+ CD40L+ memory CD4+ T cells compared to older adults. Furthermore, immune profiling data revealed younger adults had higher frequencies of circulating T follicular helper (cTfh) cells pre-vaccination and increased frequencies of activated ICOS+ CD38+ cTfh cells post-vaccination. Lastly, single-cell sequencing revealed older adults had reduced STAT1-driven antiviral gene profiles associated with activated T cell populations following stimulation with inactivated virus. Our data indicate that older adults have poor CD4+ T helper responses after vaccination despite productive antibody responses, which highlights the need to further investigate the effects of aging on CD4+ T cell responses to improve future vaccine efforts. Funding Sources R01AI142095 Topic Categories Vaccines and Immunotherapy (VAC)