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Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model

Pamela C. Proud, Daphne Tsitoura, Robert J. Watson, Brendon Y Chua, Marilyn J. Aram, Kevin R. Bewley, Breeze E. Cavell, Rebecca Cobb, Stuart Dowall, Susan A. Fotheringham, Catherine M. K. Ho, Vanessa Lucas, Didier Ngabo, Emma Rayner, Kathryn A. Ryan, Gillian S. Slack, Stephen Thomas, Nadina I. Wand, Paul Yeates, Christophe Demaison, David C. Jackson, Nathan W. Bartlett, Francesca Mercuri, Miles W. Carroll
doi: https://doi.org/10.1101/2020.09.25.309914
Pamela C. Proud
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Daphne Tsitoura
2Ena Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia
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Robert J. Watson
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Brendon Y Chua
3Department of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne, Victoria 3000, Australia
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Marilyn J. Aram
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Kevin R. Bewley
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Breeze E. Cavell
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Rebecca Cobb
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Stuart Dowall
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Susan A. Fotheringham
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Catherine M. K. Ho
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Vanessa Lucas
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Didier Ngabo
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Emma Rayner
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Kathryn A. Ryan
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Gillian S. Slack
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Stephen Thomas
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Nadina I. Wand
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Paul Yeates
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
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Christophe Demaison
2Ena Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia
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David C. Jackson
3Department of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne, Victoria 3000, Australia
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Nathan W. Bartlett
4Viral Immunology and Respiratory Disease group and Priority Research Centre for Healthy Lungs, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia
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Francesca Mercuri
2Ena Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia
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  • For correspondence: miles.carroll@phe.gov.uk fm@enarespiratory.com
Miles W. Carroll
1National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG
5Nuffield Dept of Medicine, Oxford University, Oxford, UK
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  • For correspondence: miles.carroll@phe.gov.uk fm@enarespiratory.com
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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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵7 Joint Corresponding and senior authors

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model
Pamela C. Proud, Daphne Tsitoura, Robert J. Watson, Brendon Y Chua, Marilyn J. Aram, Kevin R. Bewley, Breeze E. Cavell, Rebecca Cobb, Stuart Dowall, Susan A. Fotheringham, Catherine M. K. Ho, Vanessa Lucas, Didier Ngabo, Emma Rayner, Kathryn A. Ryan, Gillian S. Slack, Stephen Thomas, Nadina I. Wand, Paul Yeates, Christophe Demaison, David C. Jackson, Nathan W. Bartlett, Francesca Mercuri, Miles W. Carroll
bioRxiv 2020.09.25.309914; doi: https://doi.org/10.1101/2020.09.25.309914
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Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model
Pamela C. Proud, Daphne Tsitoura, Robert J. Watson, Brendon Y Chua, Marilyn J. Aram, Kevin R. Bewley, Breeze E. Cavell, Rebecca Cobb, Stuart Dowall, Susan A. Fotheringham, Catherine M. K. Ho, Vanessa Lucas, Didier Ngabo, Emma Rayner, Kathryn A. Ryan, Gillian S. Slack, Stephen Thomas, Nadina I. Wand, Paul Yeates, Christophe Demaison, David C. Jackson, Nathan W. Bartlett, Francesca Mercuri, Miles W. Carroll
bioRxiv 2020.09.25.309914; doi: https://doi.org/10.1101/2020.09.25.309914

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