Your browser doesn't support javascript.
Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model.
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.
  • Proud PC; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Tsitoura D; Ena Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia.
  • Watson RJ; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Chua BY; Department of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne, Victoria 3000, Australia.
  • Aram MJ; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Bewley KR; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Cavell BE; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Cobb R; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Dowall S; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Fotheringham SA; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Ho CMK; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Lucas V; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Ngabo D; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Rayner E; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Ryan KA; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Slack GS; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Thomas S; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Wand NI; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Yeates P; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
  • Demaison C; Ena Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia.
  • Zeng W; Department of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne, Victoria 3000, Australia.
  • Holmes I; Ena Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia.
  • Jackson DC; Department of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne, Victoria 3000, Australia.
  • Bartlett NW; Viral Immunology and Respiratory Disease group and Priority Research Centre for Healthy Lungs, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.
  • Mercuri F; Ena Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia. Electronic address: fm@enarespiratory.com.
  • Carroll MW; National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG; Nuffield Dept of Medicine, Oxford University, Oxford, UK. Electronic address: miles.carroll@phe.gov.uk.
EBioMedicine ; 63: 103153, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-956065
Semantic information from SemMedBD (by NLM)
1. Upper respiratory tract LOCATION_OF Viral Shedding
Subject
Upper respiratory tract
Predicate
LOCATION_OF
Object
Viral Shedding
2. Prophylactic treatment PREVENTS Viral Shedding
Subject
Prophylactic treatment
Predicate
PREVENTS
Object
Viral Shedding
3. Upper respiratory tract LOCATION_OF 2019 novel coronavirus
Subject
Upper respiratory tract
Predicate
LOCATION_OF
Object
2019 novel coronavirus
4. Infected PROCESS_OF Persons
Subject
Infected
Predicate
PROCESS_OF
Object
Persons
5. plaque assay MEASURES Virus Titer
Subject
plaque assay
Predicate
MEASURES
Object
Virus Titer
6. Administratio USES C0009653
Subject
Administratio
Predicate
USES
Object
C0009653
7. Upper respiratory tract LOCATION_OF Viral Shedding
Subject
Upper respiratory tract
Predicate
LOCATION_OF
Object
Viral Shedding
8. Prophylactic treatment PREVENTS Viral Shedding
Subject
Prophylactic treatment
Predicate
PREVENTS
Object
Viral Shedding
9. Upper respiratory tract LOCATION_OF 2019 novel coronavirus
Subject
Upper respiratory tract
Predicate
LOCATION_OF
Object
2019 novel coronavirus
10. Infected PROCESS_OF Persons
Subject
Infected
Predicate
PROCESS_OF
Object
Persons
11. plaque assay MEASURES Virus Titer
Subject
plaque assay
Predicate
MEASURES
Object
Virus Titer
12. Administration, Intranasal USES Condoms, Male
Subject
Administration, Intranasal
Predicate
USES
Object
Condoms, Male
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=<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.

FUNDING:

This work was funded by Ena Respiratory, Melbourne, Australia.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory System / Virus Shedding / Toll-Like Receptor 2 / Toll-Like Receptor 6 / Lipopeptides / SARS-CoV-2 Type of study: Prognostic study / Randomized controlled trials Limits: Animals Language: English Journal: EBioMedicine Year: 2021 Document Type: Article

Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory System / Virus Shedding / Toll-Like Receptor 2 / Toll-Like Receptor 6 / Lipopeptides / SARS-CoV-2 Type of study: Prognostic study / Randomized controlled trials Limits: Animals Language: English Journal: EBioMedicine Year: 2021 Document Type: Article