ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques

Nature. 2020 Oct;586(7830):578-582. doi: 10.1038/s41586-020-2608-y. Epub 2020 Jul 30.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic4. Here we show that the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated by the profiling of the IgG subclass and the expression of cytokines. Vaccination with ChAdOx1 nCoV-19 (using either a prime-only or a prime-boost regimen) induced a balanced humoral and cellular immune response of type-1 and type-2 T helper cells in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated SARS-CoV-2-infected animals. However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals. The safety, immunogenicity and efficacy profiles of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomized controlled clinical trials in humans.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Betacoronavirus / immunology*
  • Bronchoalveolar Lavage Fluid
  • COVID-19
  • COVID-19 Vaccines
  • Coronavirus Infections / genetics
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / prevention & control*
  • Coronavirus Infections / virology
  • Cytokines / immunology
  • Disease Models, Animal*
  • Female
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin G / immunology
  • Lung / immunology
  • Lung / pathology
  • Lung / virology
  • Macaca mulatta* / immunology
  • Macaca mulatta* / virology
  • Male
  • Mice
  • Pandemics / prevention & control*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / prevention & control*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • Th1 Cells / immunology
  • Vaccination
  • Viral Load
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • COVID-19 Vaccines
  • Cytokines
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • spike protein, SARS-CoV-2