Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19

Francisco Javier Salguero Bodes, Andrew D. White, Gillian S. Slack, Susan Fotheringham, Kevin R. Bewley, Karen E. Gooch, Stephanie Longet, Holly E. Humphries, Robert J. Watson, Laura Hunter, Kathryn Ryan, Yper Hall, Laura Sibley, Charlotte Sarfas, Lauren Allen, Marilyn Aram, Emily Brunt, Phillip Brown, Karen Buttigieg, Breeze E. CavellRebecca Cobb, Naomi S. Coombes, Alistair Darby, Owen Daykin-Pont, Michael J. Elmore, Isabel Garcia-Dorival, Konstantinos Gkolfinos, Kerry J. Godwin, Jade Gouriet, Rachel Halkerston, Deborah Harris, Thomas Hender, Catherine M.K. Ho, Chelsea L. Kennard, Daniel Knott, Stephanie Leung, Vanessa Lucas, Adam Mabbutt, Alexandra L. Morrison, Charlotte Nelson, Didier Ngabo, Jemma Paterson, Elizabeth J. Penn, Steven Pullan, Irene Taylor, Tom Tipton, Stephen Thomas, Julia A. Tree, Carrie Turner, Edith Vamos, Nadina Wand, Nathan R. Wiblin, Sue Charlton, Xiaofeng Dong, Bassam Hallis, Geoffrey Pearson, Emma Rayner, Andrew G. Nicholson, Simon Funnell, Julian A. Hiscox, Mike J. Dennis, Fergus V. Gleeson, Sally Sharpe, Miles Carroll*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory samples revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.

Original languageEnglish
Article number1260
Number of pages14
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 24 Feb 2021

Bibliographical note

Funding Information:
The authors would like to thank J. Druce and M.G. Catton from the Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, At the Peter Doherty Institute for Infection and Immunity, Victoria, 3000, Australia, for providing the SARS-CoV-2 isolate used in this study. This work was funded by the Coalition of Epidemic Preparedness Innovations (CEPI) and the Medical Research Council (Project CV220-060, “Development of an NHP model of infection and ADE with COVID-19 (SARS-CoV-2). The bioinformatics analysis was part supported by the US FDA contract number 75F40120C00085 ‘Characterisation of severe coronavirus infection in humans and model systems for medical countermeasure development and evaluation’ awarded to JAH and MWC.

Publisher Copyright:
© 2021, Crown.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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