AZD1222/ChAdOx1 nCoV-19 vaccination induces a polyfunctional spike protein-specific TH1 response with a diverse TCR repertoire

AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 in clinical trials and real-world studies. We characterized CD4(+) and CD8(+) T cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells from 296 unique vaccine recipients aged 18 to 85 years who enrolled in the phase 2/3 COV002 trial. Total spike protein-specific CD4(+) T cell helper type 1 (T(H)1) and CD8(+) T cell responses were increased in AZD1222-vaccinated adults of all ages after two doses of AZD1222. CD4(+) T(H)2 responses after AZD1222 vaccination were not detected. Furthermore, AZD1222-specific T(H)1 and CD8(+) T cells both displayed a high degree of polyfunctionality in all adult age groups. T cell receptor beta (TCR beta) sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for both AZD1222-induced CD4(+) and CD8(+) T cell responses. Overall, AZD1222 vaccination induced a polyfunctional T(H)1-dominated T cell response, with broad CD4(+) and CD8(+) T cell coverage across the SARS-CoV-2 spike protein.

Automated summary

AZD1222 vaccine induces effective T cell responses in adults of all age groups, mainly of T(H)1 type, covering the SARS-CoV-2 spike protein. Vaccination with AZD1222 promotes immune responses and demonstrates broad immunological protection coverage across age groups.