- Title
- Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model
- Creator
- Proud, Pamela C.; Tsitoura, Daphne; Watson, Robert J.; Chua, Brendon Y.; Aram, Marilyn J.; Bewley, Kevin R.; Cavell, Breeze E.; Cobb, Rebecca; Dowall, Stuart; Fotheringham, Susan A.; Ho, Catherine M. K.; Lucas, Vanessa; Ngabo, Didier; Rayner, Emma; Ryan, Kathryn A.; Slack, Gillian S.; Thomas, Stephen; Wand, Nadina I.; Yeates, Paul; Demaison, Christophe; Zeng, Weiguang; Holmes, Ian; Jackson, David C.; Bartlett, Nathan W.; Mercuri, Francesca; Carroll, Miles W.
- Relation
- EBioMedicine Vol. 63, January 2021, no. 103153
- Publisher Link
- http://dx.doi.org/10.1016/j.ebiom.2020.103153
- Publisher
- The Lancet Publishing Group
- Resource Type
- journal article
- Date
- 2021
- Description
- Background: The novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, 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. Methods: SARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 x 10 pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E). Findings: 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. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=<0.0001) by up to a 24 fold (96% reduction) and in nasal wash (p=0.0107) up to a 15 fold (93% reduction) in comparison to untreated animals. Interpretation: 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.
- Subject
- ferret; COVID-19; SARS-CoV-2; viral shedding; TLR-2; INNA-051; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1456762
- Identifier
- uon:45262
- Identifier
- ISSN:2352-3964
- Rights
- © 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- Language
- eng
- Full Text
- Reviewed
- Hits: 9906
- Visitors: 10031
- Downloads: 166
Collections
Goal 3: Good Health and Well-Being
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 1 MB | Adobe Acrobat PDF | View Details Download |