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

Courtney Woolsey; Viktoriya Borisevich; Abhishek Prasad; Krystle N. Agans; Daniel J. Deer; Natalie S. Dobias; John C. Heymann; Stephanie L. Foster; Corri B. Levine; Liana Medina; Kevin Melody; Joan B. Geisbert; Karla Fenton; Thomas W. Geisbert; Robert W. Cross

doi:10.1038/s41590-020-00835-8

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

Courtney Woolsey, Viktoriya Borisevich, Abhishek Prasad, Krystle N. Agans, Daniel J. Deer, Natalie S. Dobias, John C. Heymann, Stephanie L. Foster, Corri B. Levine, Liana Medina, Kevin Melody, Joan B. Geisbert, Karla Fenton, Thomas W. Geisbert, Robert W. Cross

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142 Scopus citations

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.

Original language	English (US)
Pages (from-to)	86-98
Number of pages	13
Journal	Nature Immunology
Volume	22
Issue number	1
DOIs	https://doi.org/10.1038/s41590-020-00835-8
State	Published - Jan 2021

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Woolsey, C., Borisevich, V., Prasad, A., Agans, K. N., Deer, D. J., Dobias, N. S., Heymann, J. C., Foster, S. L., Levine, C. B., Medina, L., Melody, K., Geisbert, J. B., Fenton, K., Geisbert, T. W., & Cross, R. W. (2021). Establishment of an African green monkey model for COVID-19 and protection against re-infection. Nature Immunology, 22(1), 86-98. https://doi.org/10.1038/s41590-020-00835-8

Woolsey, C, Borisevich, V, Prasad, A, Agans, KN, Deer, DJ, Dobias, NS, Heymann, JC, Foster, SL, Levine, CB, Medina, L, Melody, K, Geisbert, JB, Fenton, K, Geisbert, TW & Cross, RW 2021, 'Establishment of an African green monkey model for COVID-19 and protection against re-infection', Nature Immunology, vol. 22, no. 1, pp. 86-98. https://doi.org/10.1038/s41590-020-00835-8

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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.",

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

Abstract

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