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Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model

Authors :
Breeze E. Cavell
Marilyn Aram
Nadina Wand
Stuart D. Dowall
Susan A. Fotheringham
Daphne Tsitoura
Brendon Y. Chua
Stephen Thomas
Ian Holmes
David C. Jackson
Robert J. Watson
Pamela C. Proud
Didier Ngabo
Francesca A. Mercuri
Kevin R. Bewley
Vanessa Lucas
Kathryn A. Ryan
Gillian S. Slack
Weiguang Zeng
Christophe Demaison
Miles W. Carroll
Rebecca Cobb
Emma Rayner
Catherine M K Ho
Paul Yeates
Nathan W. Bartlett
Source :
EBioMedicine, EBioMedicine, Vol 63, Iss, Pp 103153-(2021)
Publication Year :
2021
Publisher :
Elsevier BV, 2021.

Abstract

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 × 106 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=

Details

Language :
English
ISSN :
23523964
Database :
OpenAIRE
Journal :
EBioMedicine
Accession number :
edsair.doi.dedup.....b21cacb67acae468a1e1f7b7e9cd3eae
Full Text :
https://doi.org/10.1016/j.ebiom.2020.103153