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T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial

T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2 and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18–55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.

1078-8956
270-278
Ewer, Katie J.
069f04d6-b524-45c7-ad26-ac830b990860
Barrett, Jordan R.
125813b4-dea2-45ee-a8b0-4f586347e9f6
Belij-Rammerstorfer, Sandra
a1f3ac56-807a-4221-9a1f-053fb02470b3
Sharpe, Hannah
d22eb580-7c64-40b7-a0ef-ad4d1c3606a6
Makinson, Rebecca
00fa90b9-c21b-4ecc-9963-05b6b004fa54
Morter, Richard
83c91888-fd0f-44c6-835e-6c8f46843148
Gilbert, Sarah C.
10c23e1c-6e46-4fe8-ae0b-3a1f5cf074f4
Pollard, Andrew J.
f54083f3-c730-4ecb-937e-6fb11fdd6a21
Lambe, Teresa
d5fd6770-9ef0-45a9-a23a-9a7d865009a6
the Oxford COVID Vaccine Trial Group
Ewer, Katie J.
069f04d6-b524-45c7-ad26-ac830b990860
Barrett, Jordan R.
125813b4-dea2-45ee-a8b0-4f586347e9f6
Belij-Rammerstorfer, Sandra
a1f3ac56-807a-4221-9a1f-053fb02470b3
Sharpe, Hannah
d22eb580-7c64-40b7-a0ef-ad4d1c3606a6
Makinson, Rebecca
00fa90b9-c21b-4ecc-9963-05b6b004fa54
Morter, Richard
83c91888-fd0f-44c6-835e-6c8f46843148
Gilbert, Sarah C.
10c23e1c-6e46-4fe8-ae0b-3a1f5cf074f4
Pollard, Andrew J.
f54083f3-c730-4ecb-937e-6fb11fdd6a21
Lambe, Teresa
d5fd6770-9ef0-45a9-a23a-9a7d865009a6

Ewer, Katie J., Barrett, Jordan R., Belij-Rammerstorfer, Sandra, Sharpe, Hannah, Makinson, Rebecca, Morter, Richard, Gilbert, Sarah C., Pollard, Andrew J. and Lambe, Teresa , the Oxford COVID Vaccine Trial Group (2020) T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nature Medicine, 27 (2), 270-278. (doi:10.1038/s41591-020-01194-5).

Record type: Article

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2 and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18–55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.

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More information

Accepted/In Press date: 24 November 2020
e-pub ahead of print date: 17 December 2020
Additional Information: Funding Information: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCOv-19. S.C.G. is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering the use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine. T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project. P.M.F. is a consultant to Vaccitech. A.J.P. is Chair of the UK Deptartment of Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in discussions on COVID-19 vaccines and is a member of the World Health Organization’s (WHO) Strategic Advisory Group of Experts. A.J.P. is an NIHR Senior Investigator. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, NIHR or WHO. A.V.S.H. reports personal fees from Vaccitech outside of the submitted work and has a patent for ChAdOx1 licensed to Vaccitech and might benefit from royalty income to the University of Oxford from sales of this vaccine by AstraZeneca and sublicensees. M.S. reports grants from NIHR and non-financial support from AstraZeneca during the conduct of the study; grants from Janssen; grants from GlaxoSmithKline; grants from Medimmune; grants from Novavax; grants and non-financial support from Pfizer; and grants from MCM outside of the submitted work. C.G. reports personal fees from the Duke Human Vaccine Institute outside of the submitted work. A.D.D. reports grants and personal fees from AstraZeneca outside of the submitted work. In addition, A.D.D. has a patent for the manufacturing process of ChAdOx vectors with royalties paid to AstraZeneca and a patent for ChAdOx2 vector with royalties paid to AstraZeneca. The other authors declare no competing interests. Funding Information: This work was funded by UK Research and Innovation (MC_PC_19055); the Engineering and Physical Sciences Research Council (EP/R013756/1); the Coalition for Epidemic Preparedness Innovations (CEPI); and the National Institute for Health Research (NIHR) and the NIHR Oxford Biomedical Research Centre. Additional resources for study delivery were provided by the NIHR Southampton Clinical Research Facility and the NIHR Southampton Biomedical Research Centre; University Hospital Southampton NHS Foundation Trust; the NIHR Imperial Clinical Research Facility; and the NIHR North West London, South London, Wessex and West of England Local Clinical Research Networks and the NIHR Oxford Health Biomedical Research Centre. P.M.F. received funding from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (finance code 001). Development of SARS-CoV-2 reagents was partially supported by the U.S. National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400008C. The research reagent for SARS-CoV-2 RNA (NIBSC 20/130) was obtained from the National Institute for Biological Standards and Control, UK. The control vaccine was provided free of charge by the UK Department of Health and Social Care. We received invaluable additional financial support through generous philanthropic donations to the University of Oxford, including from the Huo Family Foundation. The University of Oxford has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCov-19 (AZD1222). The authors are grateful to the senior management at AstraZeneca for facilitating and funding the manufacture of the AZD1222 vaccine candidate, the pseudovirus neutralization assays and the Meso Scale antibody assay used in this study. AstraZeneca reviewed the data from the study and the final manuscript before submission, but the authors retained editorial control. The investigators express their gratitude for the contribution of all the trial participants, the invaluable advice of the international Data Safety Monitoring Board (R. Heyderman, M. Sadarangani, S. Black, G. Bouliotis, G. Hussey, B. Ogutu, W. Orenstein, S. Ramos, C. Dekker and E. Bukusi) and the independent members of the Trial Steering Committee. We additionally acknowledge the broader support from the various teams within the University of Oxford, including the Medical Sciences Division, the Nuffield Department of Medicine (R. Cornall and O. Velicka) and the Department of Paediatrics (G. A. Holländer, J. Bagniewska, E. Derow and S. Vanderslott), the Oxford Immunology Network COVID Consortium, Clinical Trials Research Governance (H. House, C. Riddle, R. Bahadori and A. Brindle), Research Services (C. Banner and S. Pelling-Deeves), the Public Affairs Directorate (J. Colman, A. Buxton, C. McIntyre and S. Pritchard) and the Clinical Biomanufacturing Facility, as well as the Oxford University Hospitals NHS Foundation Trust (B. Holthof) and the Oxford Health NHS Foundation Trust and the trial sites. We are grateful for the input of the protein production team at the Jenner Institute. The MSD Quickplex was purchased using joint support from Versus Arthritis (grant reference 21509), Wellcome MSD ISSF (BRD00010) and the Kennedy Trust for Rheumatology Research. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care, UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, the National Institute for Health Research, the NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland’s NIHR Clinical Research Network or AstraZeneca. A.F.’s post was supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Science, China (grant number 2018-I2M-2-002). Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

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Local EPrints ID: 450683
URI: http://eprints.soton.ac.uk/id/eprint/450683
ISSN: 1078-8956
PURE UUID: 737eaed6-d424-4427-8591-01872c87c905

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Date deposited: 06 Aug 2021 16:31
Last modified: 17 Mar 2024 12:47

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Contributors

Author: Katie J. Ewer
Author: Jordan R. Barrett
Author: Sandra Belij-Rammerstorfer
Author: Hannah Sharpe
Author: Rebecca Makinson
Author: Richard Morter
Author: Sarah C. Gilbert
Author: Andrew J. Pollard
Author: Teresa Lambe
Corporate Author: the Oxford COVID Vaccine Trial Group

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