Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model
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Abstract
Respiratory viruses such as coronaviruses represent major ongoing global threats, causing epidemics and pandemics with huge economic burden. Rapid spread of virus through populations poses an enormous challenge for outbreak control. Like all respiratory viruses, the most recent novel human coronavirus SARS-CoV-2, initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission.
We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT to reduce SARS-CoV-2 transmission and provide protection against COVID-19.
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SciScore for 10.1101/2020.09.25.309914: (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 in accordance with and 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 Prior to commencing the experiment, animals were randomly assigned to the four treatment groups, to minimise bias. Blinding not detected. Power Analysis not detected. Sex as a biological variable Animals: Twenty-four healthy, female outbred ferrets (Mustela putorius furo) aged 6-8 months were obtained from a UK Home Office accredited … SciScore for 10.1101/2020.09.25.309914: (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 in accordance with and 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 Prior to commencing the experiment, animals were randomly assigned to the four treatment groups, to minimise bias. Blinding not detected. Power Analysis not detected. Sex as a biological variable Animals: Twenty-four healthy, female outbred ferrets (Mustela putorius furo) aged 6-8 months were obtained from a UK Home Office accredited supplier. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Inoculum: SARS-CoV-2 Victoria/01/202039 was generously provided by Peter Doherty Institute for Infection and Immunity, Melbourne, Australia at P1 and passaged twice in Vero/hSLAM cells [ECACC 04091501], obtained from the European Collection of Authenticated Cell Cultures ( 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)Software and Algorithms Sentences Resources Statistical analyses were performed using GraphPad Prism, version 8.4.2. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results 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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