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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.
Nat Med. 2021 02; 27(2):270-278.NMed

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.

Authors+Show Affiliations

The Jenner Institute, University of Oxford, Oxford, UK. katie.ewer@ndm.ox.ac.uk.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Nuffield Department of Medicine, University of Oxford, Oxford, UK.Clinical Biomanufacturing Facility, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.Clinical Biomanufacturing Facility, Nuffield Department of Medicine, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Clinical Biomanufacturing Facility, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.The Jenner Institute, University of Oxford, Oxford, UK. Teresa.lambe@ndm.ox.ac.uk.No affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33335323

Citation

Ewer, Katie J., et al. "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, vol. 27, no. 2, 2021, pp. 270-278.
Ewer KJ, Barrett JR, Belij-Rammerstorfer S, et al. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat Med. 2021;27(2):270-278.
Ewer, K. J., Barrett, J. R., Belij-Rammerstorfer, S., Sharpe, H., Makinson, R., Morter, R., Flaxman, A., Wright, D., Bellamy, D., Bittaye, M., Dold, C., Provine, N. M., Aboagye, J., Fowler, J., Silk, S. E., Alderson, J., Aley, P. K., Angus, B., Berrie, E., ... Lambe, T. (2021). 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. https://doi.org/10.1038/s41591-020-01194-5
Ewer KJ, et al. T Cell and Antibody Responses Induced By a Single Dose of ChAdOx1 nCoV-19 (AZD1222) Vaccine in a Phase 1/2 Clinical Trial. Nat Med. 2021;27(2):270-278. PubMed PMID: 33335323.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. AU - Ewer,Katie J, AU - Barrett,Jordan R, AU - Belij-Rammerstorfer,Sandra, AU - Sharpe,Hannah, AU - Makinson,Rebecca, AU - Morter,Richard, AU - Flaxman,Amy, AU - Wright,Daniel, AU - Bellamy,Duncan, AU - Bittaye,Mustapha, AU - Dold,Christina, AU - Provine,Nicholas M, AU - Aboagye,Jeremy, AU - Fowler,Jamie, AU - Silk,Sarah E, AU - Alderson,Jennifer, AU - Aley,Parvinder K, AU - Angus,Brian, AU - Berrie,Eleanor, AU - Bibi,Sagida, AU - Cicconi,Paola, AU - Clutterbuck,Elizabeth A, AU - Chelysheva,Irina, AU - Folegatti,Pedro M, AU - Fuskova,Michelle, AU - Green,Catherine M, AU - Jenkin,Daniel, AU - Kerridge,Simon, AU - Lawrie,Alison, AU - Minassian,Angela M, AU - Moore,Maria, AU - Mujadidi,Yama, AU - Plested,Emma, AU - Poulton,Ian, AU - Ramasamy,Maheshi N, AU - Robinson,Hannah, AU - Song,Rinn, AU - Snape,Matthew D, AU - Tarrant,Richard, AU - Voysey,Merryn, AU - Watson,Marion E E, AU - Douglas,Alexander D, AU - Hill,Adrian V S, AU - Gilbert,Sarah C, AU - Pollard,Andrew J, AU - Lambe,Teresa, AU - ,, Y1 - 2020/12/17/ PY - 2020/10/28/received PY - 2020/11/24/accepted PY - 2020/12/19/pubmed PY - 2021/2/24/medline PY - 2020/12/18/entrez SP - 270 EP - 278 JF - Nature medicine JO - Nat Med VL - 27 IS - 2 N2 - 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. SN - 1546-170X UR - https://www.unboundmedicine.com/medline/citation/33335323/T_cell_and_antibody_responses_induced_by_a_single_dose_of_ChAdOx1_nCoV_19__AZD1222__vaccine_in_a_phase_1/2_clinical_trial_ L2 - https://doi.org/10.1038/s41591-020-01194-5 DB - PRIME DP - Unbound Medicine ER -