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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.

Original publication

DOI

10.1038/s41467-020-20439-y

Type

Journal article

Journal

Nature communications

Publication Date

01/2021

Volume

12

Addresses

National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Keywords

Lung, Animals, Ferrets, Disease Models, Animal, RNA, Viral, Antibodies, Viral, Virus Replication, Virus Shedding, Dose-Response Relationship, Drug, Female, COVID-19, SARS-CoV-2, COVID-19 Vaccines