Establishment of an African green monkey model for COVID-19 and protection against re-infection

Nat Immunol. 2021 Jan;22(1):86-98. doi: 10.1038/s41590-020-00835-8. Epub 2020 Nov 24.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen vaccines and treatments. We show that African green monkeys (AGMs) support robust SARS-CoV-2 replication and develop pronounced respiratory disease, which may more accurately reflect human COVID-19 cases than other nonhuman primate species. SARS-CoV-2 was detected in mucosal samples, including rectal swabs, as late as 15 days after exposure. Marked inflammation and coagulopathy in blood and tissues were prominent features. Transcriptome analysis demonstrated stimulation of interferon and interleukin-6 pathways in bronchoalveolar lavage samples and repression of natural killer cell- and T cell-associated transcripts in peripheral blood. Despite a slight waning in antibody titers after primary challenge, enhanced antibody and cellular responses contributed to rapid clearance after re-challenge with an identical strain. These data support the utility of AGM for studying COVID-19 pathogenesis and testing medical countermeasures.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Chlorocebus aethiops
  • Disease Models, Animal*
  • Epidemics / prevention & control
  • Gene Expression / genetics
  • Gene Expression / immunology
  • Gene Expression Profiling
  • Humans
  • Interferons / genetics
  • Interferons / immunology
  • Interferons / metabolism
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Reinfection / immunology*
  • Reinfection / virology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology

Substances

  • Antibodies, Viral
  • Interferons