CD31 + naïve T cells associate with immunosenescence and responsiveness to multiple vaccines in older adults

Background: The T cell compartment undergoes significant age-related changes, contributing to the decline of the adaptive immune system and increasing the risk of suboptimal antibody responses to vaccines in older adults. To better understand the association between T cell phenotypes and vaccine responsiveness, we conducted an in-depth analysis of CD4+, CD8+, and γδ + T cells on VITAL cohort participants who are low or high responders to multiple vaccines (influenza, pneumococcal, and SARS-CoV-2). Results: Using spectral cytometry and FlowSOM, we identified detailed phenotypes of naïve, regulatory, and terminally differentiated T cells. We observed that the percentages of CD31 + naïve CD4+, CD31 + naïve CD8+, and CD38 + naïve CD8 + T cells were significantly lower in low vaccine responders. Notably, CD31 + naïve T cell subsets showed a stronger correlation with immune entropy, a measure of cumulative immune system perturbations, than with age itself. Conclusions: These findings suggest that subsets of naïve cells could be associated with weak vaccine responsiveness and immunosenescence. Furthermore, these naive T cell signatures could help predict weak vaccine responses, potentially informing targeted vaccination strategies in older adults. Clinical trial number: EudraCT: 2019-000836-24.