The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination.
Immunity
; 55(10): 1924-1939.e5, 2022 10 11.
Article
in En
| MEDLINE
| ID: mdl-35985324
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19
Limits:
Aged
/
Humans
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2022
Document type:
Article
Affiliation country:
Germany