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AZD1222/ChAdOx1 nCoV-19 vaccination induces a polyfunctional spike protein–specific TH1 response with a diverse TCR repertoire
Science Translational Medicine  (IF17.956),  Pub Date : 2021-09-30, DOI: 10.1126/scitranslmed.abj7211
Phillip A. SwansonII, Marcelino Padilla, Wesley Hoyland, Kelly McGlinchey, Paul A. Fields, Sagida Bibi, Saul N. Faust, Adrian B. McDermott, Teresa Lambe, Andrew J. Pollard, Nicholas M. Durham, Elizabeth J. Kelly, AstraZeneca/Oxford/VRC Study Group

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 (TH1) and CD8+ T cell responses were increased in AZD1222-vaccinated adults of all ages after two doses of AZD1222. CD4+ TH2 responses after AZD1222 vaccination were not detected. Furthermore, AZD1222-specific TH1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T cell receptor β (TCRβ) 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 TH1-dominated T cell response, with broad CD4+ and CD8+ T cell coverage across the SARS-CoV-2 spike protein.