Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity
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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 6 pfu) and medium (5 × 10 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 (5 × 10 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.
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SciScore for 10.1101/2020.05.29.123810: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All experimental work was conducted under the authority of a UK Home Office approved project licence that had been subject to local ethical review at PHE Porton Down by the Animal Welfare and Ethical Review Body (AWERB) as required by the Home Office Animals (Scientific Procedures) Act 1986. Randomization Experimental Design: Before the start of the experiment animals were randomly assigned to challenge groups, to minimise bias. Blinding not detected. Power Analysis not detected. Sex as a biological variable Animals: Twenty-two healthy, female ferrets ( Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Viruses … SciScore for 10.1101/2020.05.29.123810: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All experimental work was conducted under the authority of a UK Home Office approved project licence that had been subject to local ethical review at PHE Porton Down by the Animal Welfare and Ethical Review Body (AWERB) as required by the Home Office Animals (Scientific Procedures) Act 1986. Randomization Experimental Design: Before the start of the experiment animals were randomly assigned to challenge groups, to minimise bias. Blinding not detected. Power Analysis not detected. Sex as a biological variable Animals: Twenty-two healthy, female ferrets ( Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Viruses and Cells: SARS-CoV-2 Victoria/01/202026 was generously provided by The Doherty Institute, Melbourne, Australia at P1 and passaged twice in Vero/hSLAM cells [ECACC 04091501] Whole genome sequencing was performed, on the challenge isolate, using both Nanopore and Illumina as described previously40. Vero/hSLAMsuggested: ECACC Cat# 04091501, RRID:CVCL_L037)Virus titre was determined by plaque assay on Vero/E6 cells [ECACC 85020206]. Vero/E6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)SARS-CoV-2 virus plaque assay: Samples were diluted in serum-free MEM containing antibiotic/antimycotic (Life Technologies) and incubated in 24-well plates (Nunc, ThermoFisher Scientific, Loughborough, UK) with Vero E6 cell monolayers. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources Viruses and Cells: SARS-CoV-2 Victoria/01/202026 was generously provided by The Doherty Institute, Melbourne, Australia at P1 and passaged twice in Vero/hSLAM cells [ECACC 04091501] Whole genome sequencing was performed, on the challenge isolate, using both Nanopore and Illumina as described previously40. Nanoporesuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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