Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity

Kathryn A. Ryan, Kevin R. Bewley, Susan A. Fotheringham, Gillian S. Slack, Phillip Brown, Yper Hall, Nadina I. Wand, Anthony C. Marriott, Breeze E. Cavell, Julia A. Tree, Lauren Allen, Marilyn J. Aram, Thomas J. Bean, Emily Brunt, Karen R. Buttigieg, Daniel P. Carter, Rebecca Cobb, Naomi S. Coombes, Steve J. Findlay-Wilson, Kerry J. GodwinKaren E. Gooch, Jade Gouriet, Rachel Halkerston, Debbie J. Harris, Thomas H. Hender, Holly E. Humphries, Laura Hunter, Catherine M.K. Ho, Chelsea L. Kennard, Stephanie Leung, Stephanie Longet, Didier Ngabo, Karen L. Osman, Jemma Paterson, Elizabeth J. Penn, Steven Pullan, Emma Rayner, Oliver Skinner, Kimberley Steeds, Irene Taylor, Tom Tipton, Stephen Thomas, Carrie Turner, Robert J. Watson, Nathan R. Wiblin, Sue Charlton, Bassam Hallis, Julian A. Hiscox, Simon Funnell, Mike J. Dennis, Catherine J. Whittaker, Michael G. Catton, Julian Druce, Francisco Javier Salguero Bodes, Miles Carroll*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)
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Abstract

There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5x10(6)pfu) and medium (5x10(4)pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5x10(2)pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease. SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

Original languageEnglish
Article number81
Number of pages13
JournalNature Communications
Volume12
Issue number1
Early online date4 Jan 2021
DOIs
Publication statusPublished - 4 Jan 2021

Bibliographical note

Funding Information:
The authors gratefully acknowledge the support from the Biological Investigations Group at the National Infection Service, PHE, Porton Down, UK. The views expressed in this paper are those of the authors and not necessarily those of the funding body. This work was funded by the US Food and Drug Administration [Contract number: HHSF223201710194C].

Open Access: This article is licensed under a Creative Commons Attribution
4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Publisher Copyright: © Crown 2021

Citation: Ryan, K.A., Bewley, K.R., Fotheringham, S.A. et al. Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity. Nat Commun 12, 81 (2021).

DOI: https://doi.org/10.1038/s41467-020-20439-y

Keywords

  • ACUTE RESPIRATORY SYNDROME
  • INFLUENZA-VIRUS PATHOGENESIS
  • SARS CORONAVIRUS INFECTION
  • ANIMAL-MODELS
  • TRANSMISSION
  • VACCINE
  • CATS
  • MICE

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