Comparison of Rhesus and Cynomolgus macaques as an authentic model for COVID-19

Author:

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

Abstract

ABSTRACTA 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 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, resembling the mild clinical cases of COVID-19 in humans. Immune responses against SARS-CoV-2 were also similar in both species and equivalent to those reported in milder infections and convalescent human patients. Importantly, we have devised 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 optimal 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 novel and repurposed interventions against SARS-CoV-2. Accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.

Publisher

Cold Spring Harbor Laboratory

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