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

KJ Ewer, JR Barrett, S Belij-Rammerstorfer, H Sharpe… - Nature medicine, 2021 - nature.com
Nature medicine, 2021nature.com
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 needed 1. Strong, Th1-skewed T cell responses can drive protective
humoral and cell-mediated immune responses 2 and might reduce the potential for disease
enhancement 3. Cytotoxic T cells clear virus-infected host cells and contribute to control of
infection 4. Studies of patients infected with SARS-CoV-2 have suggested a protective role …
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 needed 1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses 2 and might reduce the potential for disease enhancement 3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection 4. 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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