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



Ryan, Kathryn A ORCID: 0000-0001-8608-1144, Bewley, Kevin R ORCID: 0000-0002-9078-6734, Fotheringham, Susan A, Slack, Gillian S, Brown, Phillip ORCID: 0000-0001-6367-6495, Hall, Yper, Wand, Nadina I ORCID: 0000-0002-5518-4367, Marriott, Anthony C ORCID: 0000-0002-8862-9852, Cavell, Breeze E ORCID: 0000-0001-9897-1590, Tree, Julia A
et al (show 45 more authors) (2021) Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity. Nature communications, 12 (1). 81 - ?.

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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 × 10<sup>6</sup> pfu) and medium (5 × 10<sup>4</sup> 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 × 10<sup>2</sup> 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.

Item Type: Article
Uncontrolled 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
Depositing User: Symplectic Admin
Date Deposited: 15 Jan 2021 09:21
Last Modified: 05 Mar 2021 15:10
DOI: 10.1038/s41467-020-20439-y
Open Access URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC77824...
URI: https://livrepository.liverpool.ac.uk/id/eprint/3113641