Ryan KA., Bewley KR., Fotheringham SA., Slack GS., Brown P., Hall Y., Wand NI., Marriott AC., Cavell BE., Tree JA., Allen L., Aram MJ., Bean TJ., Brunt E., Buttigieg KR., Carter DP., Cobb R., Coombes NS., Findlay-Wilson SJ., Godwin KJ., Gooch KE., Gouriet J., Halkerston R., Harris DJ., Hender TH., Humphries HE., Hunter L., Ho CMK., Kennard CL., Leung S., Longet S., Ngabo D., Osman KL., Paterson J., Penn EJ., Pullan ST., Rayner E., Skinner O., Steeds K., Taylor I., Tipton T., Thomas S., Turner C., Watson RJ., Wiblin NR., Charlton S., Hallis B., Hiscox JA., Funnell S., Dennis MJ., Whittaker CJ., Catton MG., Druce J., Salguero FJ., Carroll MW.

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.

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

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