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

• DOI: 10.1038/s41467-020-20439-y
• Publication Date: 2021-01-04T11:02:41Z
• Authors: Kathryn A. Ryan; Kevin R. Bewley; Susan A. Fotherin...; 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-...; 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. Whit...; Michael G. Catton; Julian Druce; Francisco J. Salg...; Miles W. Carroll
• Keywords: 2019-20 coronavirus outbreak; Sars virus; Coronavirus Infections

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 dose titration study SARS-CoV-2 in ferret model. After high (5 × 106 pfu) medium 104 virus delivered, intranasally, viral RNA shedding upper respiratory tract (URT) observed 6/6 animals, however, only 1/6 ferrets show similar signs after low 102 challenge. Following sequential culls pathological mild multifocal bronchopneumonia approximately 5-15% lung seen on day 3, dosed groups. Ferrets re-challenged, ceased, are fully protected from acute pathology. The endpoints URT replication & distinct pathology most consistently group. This model infection presents clinical disease.