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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. Godwin, Karen 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 T. 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 J. Salguero and Miles W. Carroll ()
Additional contact information
Kathryn A. Ryan: National Infection Service, Public Health England (PHE)
Kevin R. Bewley: National Infection Service, Public Health England (PHE)
Susan A. Fotheringham: National Infection Service, Public Health England (PHE)
Gillian S. Slack: National Infection Service, Public Health England (PHE)
Phillip Brown: National Infection Service, Public Health England (PHE)
Yper Hall: National Infection Service, Public Health England (PHE)
Nadina I. Wand: National Infection Service, Public Health England (PHE)
Anthony C. Marriott: National Infection Service, Public Health England (PHE)
Breeze E. Cavell: National Infection Service, Public Health England (PHE)
Julia A. Tree: National Infection Service, Public Health England (PHE)
Lauren Allen: National Infection Service, Public Health England (PHE)
Marilyn J. Aram: National Infection Service, Public Health England (PHE)
Thomas J. Bean: National Infection Service, Public Health England (PHE)
Emily Brunt: National Infection Service, Public Health England (PHE)
Karen R. Buttigieg: National Infection Service, Public Health England (PHE)
Daniel P. Carter: National Infection Service, Public Health England (PHE)
Rebecca Cobb: National Infection Service, Public Health England (PHE)
Naomi S. Coombes: National Infection Service, Public Health England (PHE)
Steve J. Findlay-Wilson: National Infection Service, Public Health England (PHE)
Kerry J. Godwin: National Infection Service, Public Health England (PHE)
Karen E. Gooch: National Infection Service, Public Health England (PHE)
Jade Gouriet: National Infection Service, Public Health England (PHE)
Rachel Halkerston: National Infection Service, Public Health England (PHE)
Debbie J. Harris: National Infection Service, Public Health England (PHE)
Thomas H. Hender: National Infection Service, Public Health England (PHE)
Holly E. Humphries: National Infection Service, Public Health England (PHE)
Laura Hunter: National Infection Service, Public Health England (PHE)
Catherine M. K. Ho: National Infection Service, Public Health England (PHE)
Chelsea L. Kennard: National Infection Service, Public Health England (PHE)
Stephanie Leung: National Infection Service, Public Health England (PHE)
Stephanie Longet: National Infection Service, Public Health England (PHE)
Didier Ngabo: National Infection Service, Public Health England (PHE)
Karen L. Osman: National Infection Service, Public Health England (PHE)
Jemma Paterson: National Infection Service, Public Health England (PHE)
Elizabeth J. Penn: National Infection Service, Public Health England (PHE)
Steven T. Pullan: National Infection Service, Public Health England (PHE)
Emma Rayner: National Infection Service, Public Health England (PHE)
Oliver Skinner: National Infection Service, Public Health England (PHE)
Kimberley Steeds: National Infection Service, Public Health England (PHE)
Irene Taylor: National Infection Service, Public Health England (PHE)
Tom Tipton: National Infection Service, Public Health England (PHE)
Stephen Thomas: National Infection Service, Public Health England (PHE)
Carrie Turner: National Infection Service, Public Health England (PHE)
Robert J. Watson: National Infection Service, Public Health England (PHE)
Nathan R. Wiblin: National Infection Service, Public Health England (PHE)
Sue Charlton: National Infection Service, Public Health England (PHE)
Bassam Hallis: National Infection Service, Public Health England (PHE)
Julian A. Hiscox: University of Liverpool
Simon Funnell: National Infection Service, Public Health England (PHE)
Mike J. Dennis: National Infection Service, Public Health England (PHE)
Catherine J. Whittaker: National Infection Service, Public Health England (PHE)
Michael G. Catton: Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity
Julian Druce: Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity
Francisco J. Salguero: National Infection Service, Public Health England (PHE)
Miles W. Carroll: National Infection Service, Public Health England (PHE)

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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 (5 × 106 pfu) and medium (5 × 104 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 (5 × 102 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.

Date: 2021
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Citations: View citations in EconPapers (3)

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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20439-y

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DOI: 10.1038/s41467-020-20439-y

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