The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination

C Saggau, GR Martini, E Rosati, S Meise, B Messner… - Immunity, 2022 - cell.com
C Saggau, GR Martini, E Rosati, S Meise, B Messner, AK Kamps, N Bekel, J Gigla, R Rose…
Immunity, 2022cell.com
SARS-CoV-2 infection and vaccination generates enormous host-response heterogeneity
and an age-dependent loss of immune-response quality. How the pre-exposure T cell
repertoire contributes to this heterogeneity is poorly understood. We combined analysis of
SARS-CoV-2-specific CD4+ T cells pre-and post-vaccination with longitudinal T cell receptor
tracking. We identified strong pre-exposure T cell variability that correlated with subsequent
immune-response quality and age. High-quality responses, defined by strong expansion of …
Summary
SARS-CoV-2 infection and vaccination generates enormous host-response heterogeneity and an age-dependent loss of immune-response quality. How the pre-exposure T cell repertoire contributes to this heterogeneity is poorly understood. We combined analysis of SARS-CoV-2-specific CD4+ T cells pre- and post-vaccination with longitudinal T cell receptor tracking. We identified strong pre-exposure T cell variability that correlated with subsequent immune-response quality and age. High-quality responses, defined by strong expansion of high-avidity spike-specific T cells, high interleukin-21 production, and specific immunoglobulin G, depended on an intact naive repertoire and exclusion of pre-existing memory T cells. In the elderly, T cell expansion from both compartments was severely compromised. Our results reveal that an intrinsic defect of the CD4+ T cell repertoire causes the age-dependent decline of immune-response quality against SARS-CoV-2 and highlight the need for alternative strategies to induce high-quality T cell responses against newly arising pathogens in the elderly.
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