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T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire

T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire
T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-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 (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.

Swanson, Phillip A
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Padilla, Marcelino
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Hoyland, Wesley
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McGlinchey, Kelly
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Fields, Paul A
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Bibi, Sagida
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Faust, Saul N
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McDermott, Adrian B
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Lambe, Teresa
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Pollard, Andrew J
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Durham, Nicholas M
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Kelly, Elizabeth J
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Swanson, Phillip A
49e02ec6-c47b-4bad-aa69-49aa6c366de1
Padilla, Marcelino
cdd322f0-8831-4ecf-a559-97187274e471
Hoyland, Wesley
a9bf5046-6200-48fe-b0a1-c85ac98a2820
McGlinchey, Kelly
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Fields, Paul A
3eec7546-d805-46d4-a82c-3dc9145cb7a8
Bibi, Sagida
bd84c45a-68e3-47a1-b5ea-20b41042e9bf
Faust, Saul N
f97df780-9f9b-418e-b349-7adf63e150c1
McDermott, Adrian B
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Lambe, Teresa
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Pollard, Andrew J
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Durham, Nicholas M
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Kelly, Elizabeth J
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Swanson, Phillip A, Padilla, Marcelino, Hoyland, Wesley, McGlinchey, Kelly, Fields, Paul A, Bibi, Sagida, Faust, Saul N, McDermott, Adrian B, Lambe, Teresa, Pollard, Andrew J, Durham, Nicholas M and Kelly, Elizabeth J (2021) T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire. medRxiv. (doi:10.1101/2021.06.17.21259027).

Record type: Article

Abstract

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.

Text
2021.06.17.21259027v2.full - Author's Original
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More information

Accepted/In Press date: 13 July 2021
Published date: 13 July 2021
Additional Information: medRxiv pre-print : ineligible publication type for NIHR reporting

Identifiers

Local EPrints ID: 457147
URI: http://eprints.soton.ac.uk/id/eprint/457147
PURE UUID: bda0d392-7093-4d89-984c-a238532137a0
ORCID for Saul N Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 24 May 2022 17:03
Last modified: 17 Mar 2024 03:06

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Contributors

Author: Phillip A Swanson
Author: Marcelino Padilla
Author: Wesley Hoyland
Author: Kelly McGlinchey
Author: Paul A Fields
Author: Sagida Bibi
Author: Saul N Faust ORCID iD
Author: Adrian B McDermott
Author: Teresa Lambe
Author: Andrew J Pollard
Author: Nicholas M Durham
Author: Elizabeth J Kelly

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