T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire.
Swanson PA., Padilla M., Hoyland W., McGlinchey K., Fields PA., Bibi S., Faust SN., McDermott AB., Lambe T., Pollard AJ., Durham NM., Kelly EJ., Study Group None., Adlou S., Aley PK., Angus B., Anslow R., Baker P., Bansal H., Beveridge A., Bridges-Webb A., Ching S., Cicconi P., Clutterbuck EA., Collins AM., Darton TC., Demissie T., Dinesh T., Douglas AD., Duncan CJA., Ewer KJ., Felle S., Finn A., Folegatti PM., Fuskova M., Gilbert SC., Goodman A., Green CA., Harbolick E., Hart TC., Hayes S., Hill AVS., Jenkin D., Jepson BM., Kasanyinga M., Kerridge S., Libri V., Lillie PJ., McGregor AC., Minassian AM., Mujadidi YF., Pilataxi F., Plested E., Provstgaard-Morys S., Ramasamy M., Robinson H., Sanders K., Smith A., Snape MD., Song R., Sutherland RK., Thomson EC., Toshner M., Turner DPJ., Voysey M., Williams CJ.
AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and CD8+ T-cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells (PBMCs) from 280 unique vaccine recipients aged 18-85 years who enrolled in the phase 2/3 COV002 trial. Total spike-specific CD4+ T cell helper type 1 (Th1) and CD8+ T-cell responses were significantly increased in AZD1222-vaccinated adults of all ages following two doses of AZD1222. CD4+ Th2 responses following 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 (TCR) β 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 the AZD1222-induced CD4+ and CD8+ T-cell responses. Overall, AZD1222 vaccination induced a robust, polyfunctional Th1-dominated T-cell response, with broad CD4+ and CD8+ T-cell coverage across the SARS-CoV-2 spike protein. One Sentence Summary: Polyfunctional CD4+ and CD8+ T-cell responses are elicited against the SARS-CoV-2 spike protein following vaccination with AZD1222.