Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity
- Ryan, Kathryn A
- Bewley, Kevin R
- Fotheringham, Susan A
- Slack, Gillian S
- Brown, Phillip
- Hall, Yper
- Wand, Nadina I
- Marriott, Anthony C
- Cavell, Breeze E
- Tree, Julia A
- Allen, Lauren
- Aram, Marilyn J
- Bean, Thomas J
- Brunt, Emily
- Buttigieg, Karen R
- Carter, Daniel P
- Cobb, Rebecca
- Coombes, Naomi S
- Findlay-Wilson, Steve J
- Godwin, Kerry J
- Gooch, Karen E
- Gouriet, Jade
- Halkerston, Rachel
- Harris, Debbie J
- Hender, Thomas H
- Humphries, Holly E
- Hunter, Laura
- Ho, Catherine MK
- Kennard, Chelsea L
- Leung, Stephanie
- Longet, Stephanie
- Ngabo, Didier
- Osman, Karen L
- Paterson, Jemma
- Penn, Elizabeth J
- Pullan, Steven T
- Rayner, Emma
- Skinner, Oliver
- Steeds, Kimberley
- Taylor, Irene
- Tipton, Tom
- Thomas, Stephen
- Turner, Carrie
- Watson, Robert J
- Wiblin, Nathan R
- Charlton, Sue
- Hallis, Bassam
- Hiscox, Julian A
- Funnell, Simon
- Dennis, Mike J
- Whittaker, Catherine J
- Catton, Michael G
- Druce, Julian
- Salguero, Francisco J
- Carroll, Miles W
DOIAbstract
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 endpoi...
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