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 Feb;27(2):270-278. doi: 10.1038/s41591-020-01194-5. Epub 2020 Dec 17.

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.

Publication types

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

MeSH terms

  • Adolescent
  • Antibody Formation / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 / immunology
  • COVID-19 / virology
  • COVID-19 Vaccines / immunology*
  • Dose-Response Relationship, Immunologic
  • Female
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin A / immunology
  • Immunoglobulin M / immunology
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Protein Subunits / immunology
  • SARS-CoV-2 / immunology
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocytes / immunology*
  • Vaccination
  • Young Adult

Substances

  • COVID-19 Vaccines
  • Immunoglobulin A
  • Immunoglobulin M
  • Protein Subunits
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Interferon-gamma
  • ChAdOx1 COVID-19 vaccine

Associated data

  • ClinicalTrials.gov/NCT04400838