Histopathological and Immunological Findings in the Common Marmoset Following Exposure to Aerosolized SARS-CoV-2

Rachel E. Ireland*, Carwyn D. Davies, Emma Keyser, James S.F. Findlay, Lin Eastaugh, Thomas R. Laws, Francisco J. Salguero, Laura Hunter, Michelle Nelson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

There is an enduring requirement to develop animal models of COVID-19 to assess the efficacy of vaccines and therapeutics that can be used to treat the disease in humans. In this study, six marmosets were exposed to a small particle aerosol (1–3 µm) of SARS-CoV-2 VIC01 that delivered the virus directly to the lower respiratory tract. Following the challenge, marmosets did not develop clinical signs, although a disruption to the normal diurnal temperature rhythm was observed in three out of six animals. Early weight loss and changes to respiratory pattern and activity were also observed, yet there was limited evidence of viral replication or lung pathology associated with infection. There was a robust innate immunological response to infection, which included an early increase in circulating neutrophils and monocytes and a reduction in the proportion of circulating T-cells. Expression of the ACE2 receptor in respiratory tissues was almost absent, but there was ubiquitous expression of TMPRSS2. The results of this study indicate that exposure of marmosets to high concentrations of aerosolised SARS-CoV-2 did not result in the development of clear, reproducible signs of COVID-19.

Original languageEnglish
Article number1580
JournalViruses
Volume14
Issue number7
DOIs
Publication statusPublished - Jul 2022
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported through funding from The Coalition for Epidemic Preparedness Innovations (CEPI) under project 710915, through an implementing partnership to Dstl for modelling and vaccine testing.

Funding Information:
We thank CEPI, and especially Amy Shurtleff, William Dowling, and Carolyn Clark, for funding the work and all our colleagues at Dstl who supported this work in many ways. Dstl would like to acknowledge the University of Melbourne, Victoria 3010 Australia for the kind supply of the SARS-CoV-2 virus (BetaCoV/Australia/VIC01/2020). Dstl would also like to thank Neil Almond and Neil Berry from National Institute for Biological Controls and Standards (NIBSC) for conducting the sequencing of the viral stocks.

Publisher Copyright:
© 2022 by the authors.

Keywords

  • ACE2
  • aerosol
  • marmoset
  • SARS-CoV-2
  • TMPRSS2

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