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

SARS-CoV-2, the causative agent of COVID-19, has caused a global pandemic and safe, effective vaccines are urgently needed. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses, and may reduce the potential for disease enhancement. Cytotoxic T cells cle...

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Main Authors: Ewer, K, Barrett, J, Belij-Rammerstorfer, S, Lambe, T, Hill, A, Pollard, A, Gilbert, S, Et al.
Other Authors: Oxford COVID Vaccine Trial Group
Format: Journal article
Language:English
Published: Springer Nature 2020
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author Ewer, K
Barrett, J
Belij-Rammerstorfer, S
Lambe, T
Hill, A
Pollard, A
Gilbert, S
Et al.
author2 Oxford COVID Vaccine Trial Group
author_facet Oxford COVID Vaccine Trial Group
Ewer, K
Barrett, J
Belij-Rammerstorfer, S
Lambe, T
Hill, A
Pollard, A
Gilbert, S
Et al.
author_sort Ewer, K
collection OXFORD
description SARS-CoV-2, the causative agent of COVID-19, has caused a global pandemic and safe, effective vaccines are urgently needed. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses, and may reduce the potential for disease enhancement. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cellmediated immune responses in recovery from COVID-19. 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) given as either a one or two dose regimen. The vaccine was tolerated, with induction of neutralising 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 eight weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterised by IFN-γ and TNFα 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 favourable 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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spelling oxford-uuid:6bb31ae7-cb7b-4e54-b9df-bca436d1290b2022-03-26T19:05:50ZT cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a Phase 1/2 clinical trialJournal articlehttp://purl.org/coar/resource_type/c_545buuid:6bb31ae7-cb7b-4e54-b9df-bca436d1290bEnglishSymplectic ElementsSpringer Nature2020Ewer, KBarrett, JBelij-Rammerstorfer, SLambe, THill, APollard, AGilbert, SEt al.Oxford COVID Vaccine Trial GroupSARS-CoV-2, the causative agent of COVID-19, has caused a global pandemic and safe, effective vaccines are urgently needed. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses, and may reduce the potential for disease enhancement. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cellmediated immune responses in recovery from COVID-19. 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) given as either a one or two dose regimen. The vaccine was tolerated, with induction of neutralising 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 eight weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterised by IFN-γ and TNFα 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 favourable 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.
spellingShingle Ewer, K
Barrett, J
Belij-Rammerstorfer, S
Lambe, T
Hill, A
Pollard, A
Gilbert, 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
title T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a Phase 1/2 clinical trial
title_full T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a Phase 1/2 clinical trial
title_fullStr T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a Phase 1/2 clinical trial
title_full_unstemmed T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a Phase 1/2 clinical trial
title_short T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a Phase 1/2 clinical trial
title_sort t cell and antibody responses induced by a single dose of chadox1 ncov 19 azd1222 vaccine in a phase 1 2 clinical trial
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