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 (5x10(6)pfu) and medium (5x10(4)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 (5x10(2)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.
Bibliographical noteFunding Information:
The authors gratefully acknowledge the support from the Biological Investigations Group at the National Infection Service, PHE, Porton Down, UK. The views expressed in this paper are those of the authors and not necessarily those of the funding body. This work was funded by the US Food and Drug Administration [Contract number: HHSF223201710194C].
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Publisher Copyright: © Crown 2021
Citation: Ryan, K.A., Bewley, K.R., Fotheringham, S.A. et al. Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity. Nat Commun 12, 81 (2021).
- ACUTE RESPIRATORY SYNDROME
- INFLUENZA-VIRUS PATHOGENESIS
- SARS CORONAVIRUS INFECTION