Neutralizing antibody-dependent and -independent immune responses against SARS-CoV-2 in cynomolgus macaques

Virology. 2021 Feb:554:97-105. doi: 10.1016/j.virol.2020.12.013. Epub 2020 Dec 29.

Abstract

We examined the pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in cynomolgus macaques for 28 days to establish an animal model of COVID-19 for the development of vaccines and antiviral drugs. Cynomolgus macaques infected with SARS-CoV-2 showed body temperature rises and X-ray radiographic pneumonia without life-threatening clinical signs of disease. A neutralizing antibody against SARS-CoV-2 and T-lymphocytes producing interferon (IFN)-γ specifically for SARS-CoV-2 N-protein were detected on day 14 in one of three macaques with viral pneumonia. In the other two macaques, in which a neutralizing antibody was not detected, T-lymphocytes producing IFN-γ specifically for SARS-CoV-2 N protein increased on day 7 to day 14, suggesting that not only a neutralizing antibody but also cellular immunity has a role in the elimination of SARS-CoV-2. Thus, because of similar symptoms to approximately 80% of patients, cynomolgus macaques are appropriate to extrapolate the efficacy of vaccines and antiviral drugs for humans.

Keywords: Neutralizing antibody; Nonhuman primate; Pneumonia; SARS-CoV-2; Th1 response; Thrombus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Cytokines / blood
  • Disease Models, Animal*
  • Female
  • Interferon-gamma / immunology
  • Macaca fascicularis
  • Male
  • Mouth / virology
  • Nasal Cavity / virology
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / pathogenicity
  • SARS-CoV-2 / physiology
  • T-Lymphocytes / immunology*
  • Viral Load

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines
  • Interferon-gamma