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. Cavell; Rebecca 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

doi:10.1038/s41467-021-21389-9

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 journal › Article › peer-review

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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 language	English
Article number	1260
Number of pages	14
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-21389-9
Publication status	Published - 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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Salguero Bodes, F. J., White, A. D., Slack, G. S., Fotheringham, S., Bewley, K. R., Gooch, K. E., Longet, S., Humphries, H. E., Watson, R. J., Hunter, L., Ryan, K., Hall, Y., Sibley, L., Sarfas, C., Allen, L., Aram, M., Brunt, E., Brown, P., Buttigieg, K., ... Carroll, M. (2021). Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19. Nature Communications, 12(1), Article 1260. https://doi.org/10.1038/s41467-021-21389-9

@article{eaf723068b9a499b93313d88ab096b68,

title = "Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19",

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.",

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

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 {\textquoteleft}Characterisation of severe coronavirus infection in humans and model systems for medical countermeasure development and evaluation{\textquoteright} awarded to JAH and MWC. Publisher Copyright: {\textcopyright} 2021, Crown. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

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day = "24",

doi = "10.1038/s41467-021-21389-9",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

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Salguero Bodes, FJ , White, AD, Slack, GS, Fotheringham, S , Bewley, KR , Gooch, KE, Longet, S, Humphries, HE, Watson, RJ, Hunter, L , Ryan, K , Hall, Y, Sibley, L, Sarfas, C , Allen, L, Aram, M, Brunt, E, Brown, P , Buttigieg, K , Cavell, BE, Cobb, R, Coombes, NS, Darby, A, Daykin-Pont, O, Elmore, MJ, Garcia-Dorival, I, Gkolfinos, K, Godwin, KJ, Gouriet, J, Halkerston, R, Harris, D, Hender, T, Ho, CMK, Kennard, CL, Knott, D, Leung, S, Lucas, V, Mabbutt, A, Morrison, AL, Nelson, C, Ngabo, D, Paterson, J, Penn, EJ, Pullan, S, Taylor, I, Tipton, T, Thomas, S , Tree, JA , Turner, C, Vamos, E, Wand, N, Wiblin, NR, Charlton, S, Dong, X, Hallis, B, Pearson, G, Rayner, E, Nicholson, AG, Funnell, S, Hiscox, JA, Dennis, MJ, Gleeson, FV, Sharpe, S & Carroll, M 2021, 'Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19', Nature Communications, vol. 12, no. 1, 1260. https://doi.org/10.1038/s41467-021-21389-9

TY - JOUR

T1 - Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19

AU - Salguero Bodes, Francisco Javier

AU - White, Andrew D.

AU - Slack, Gillian S.

AU - Fotheringham, Susan

AU - Bewley, Kevin R.

AU - Gooch, Karen E.

AU - Longet, Stephanie

AU - Humphries, Holly E.

AU - Watson, Robert J.

AU - Hunter, Laura

AU - Ryan, Kathryn

AU - Hall, Yper

AU - Sibley, Laura

AU - Sarfas, Charlotte

AU - Allen, Lauren

AU - Aram, Marilyn

AU - Brunt, Emily

AU - Brown, Phillip

AU - Buttigieg, Karen

AU - Cavell, Breeze E.

AU - Cobb, Rebecca

AU - Coombes, Naomi S.

AU - Darby, Alistair

AU - Daykin-Pont, Owen

AU - Elmore, Michael J.

AU - Garcia-Dorival, Isabel

AU - Gkolfinos, Konstantinos

AU - Godwin, Kerry J.

AU - Gouriet, Jade

AU - Halkerston, Rachel

AU - Harris, Deborah

AU - Hender, Thomas

AU - Ho, Catherine M.K.

AU - Kennard, Chelsea L.

AU - Knott, Daniel

AU - Leung, Stephanie

AU - Lucas, Vanessa

AU - Mabbutt, Adam

AU - Morrison, Alexandra L.

AU - Nelson, Charlotte

AU - Ngabo, Didier

AU - Paterson, Jemma

AU - Penn, Elizabeth J.

AU - Pullan, Steven

AU - Taylor, Irene

AU - Tipton, Tom

AU - Thomas, Stephen

AU - Tree, Julia A.

AU - Turner, Carrie

AU - Vamos, Edith

AU - Wand, Nadina

AU - Wiblin, Nathan R.

AU - Charlton, Sue

AU - Dong, Xiaofeng

AU - Hallis, Bassam

AU - Pearson, Geoffrey

AU - Rayner, Emma

AU - Nicholson, Andrew G.

AU - Funnell, Simon

AU - Hiscox, Julian A.

AU - Dennis, Mike J.

AU - Gleeson, Fergus V.

AU - Sharpe, Sally

AU - Carroll, Miles

N1 - 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.

PY - 2021/2/24

Y1 - 2021/2/24

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-021-21389-9

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SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

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M1 - 1260

ER -

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

Abstract

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