1. Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity
- Author
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Sue Charlton, Julian Druce, Bassam Hallis, Robert J. Watson, Tom Tipton, Julia A. Tree, Naomi Coombes, Thomas Hender, Simon G. P. Funnell, Elizabeth J Penn, Emily Brunt, Gillian S. Slack, Kimberley Steeds, Stephanie Longet, Chelsea L Kennard, Stephanie Leung, Daniel P. Carter, Rebecca Cobb, Marilyn Aram, Breeze E. Cavell, Thomas Bean, Nathan R Wiblin, Laura Hunter, Karen L. Osman, Francisco J. Salguero, Anthony C. Marriott, Karen R. Buttigieg, Miles W. Carroll, Kevin R. Bewley, Holly E. Humphries, Kathryn A. Ryan, Phillip Brown, Kerry J Godwin, Michael G Catton, Emma Rayner, Carrie Turner, Julian A. Hiscox, Steve J. Findlay-Wilson, Nadina Wand, Yper Hall, Didier Ngabo, Rachel Halkerston, Susan A. Fotheringham, Jade Gouriet, Catherine J. Whittaker, Stephen Thomas, Irene Taylor, Mike Dennis, Karen E. Gooch, Oliver Skinner, Catherine M K Ho, Jemma Paterson, Steven T. Pullan, Lauren Allen, and Debbie J Harris
- Subjects
0301 basic medicine ,COVID-19 Vaccines ,Science ,viruses ,030106 microbiology ,General Physics and Astronomy ,Antibodies, Viral ,Virus Replication ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Article ,03 medical and health sciences ,medicine ,Animals ,Viral shedding ,Lung ,Multidisciplinary ,biology ,Dose-Response Relationship, Drug ,business.industry ,SARS-CoV-2 ,Ferrets ,RNA ,virus diseases ,COVID-19 ,General Chemistry ,respiratory system ,Virus Shedding ,Dose–response relationship ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,biology.protein ,RNA, Viral ,Nasal administration ,Female ,Antibody ,business ,Infection ,Respiratory tract - 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., 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.
- Published
- 2021