Evidence map›Paper›PMID 33279857›Full record

ArticleEBioMedicine2021

Prophylactic intranasal administration of a TLR2/6 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 and 16 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 1 pooled it
11.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.

  1. Innate immunity to SARS-CoV-2 infection: a review.Epidemiology and infection · 2022
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Upper respiratory tract immunization with PamFrontiers in immunology · 2025
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. TLRs: Innate Immune Sentries against SARS-CoV-2 Infection.International journal of molecular sciences · 2023
    Review
  19. Article
  20. Review

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 5 institutions in 2 countries.

Pamela C ProudNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Daphne TsitouraEna Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia.
Robert J WatsonNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Brendon Y ChuaDepartment of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne, Victoria 3000, Australia.
Marilyn J AramNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Kevin R BewleyNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Breeze E CavellNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Rebecca CobbNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Stuart DowallNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Susan A FotheringhamNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Catherine M K HoNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Vanessa LucasNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Didier NgaboNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Emma RaynerNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Kathryn A RyanNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Gillian S SlackNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Stephen ThomasNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Nadina I WandNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Paul YeatesNational Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JG.
Christophe DemaisonEna Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia.
Weiguang ZengDepartment of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne, Victoria 3000, Australia.
Ian HolmesEna Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia.
David C JacksonDepartment of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne, Victoria 3000, Australia.
Nathan W BartlettViral Immunology and Respiratory Disease group and Priority Research Centre for Healthy Lungs, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.
Francesca MercuriEna Respiratory, Level 9, 31 Queen St, Melbourne, Victoria, 3000, Australia. Electronic address: fm@enarespiratory.com.
Miles W CarrollNational 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.
Public Health England · GBRespiratory Clinical Trials · AUThe University of Melbourne · AUHunter Medical Research Institute · AURoyal Dental Hospital of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe 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.

methodsSARS-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 × 10

findingsWe 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.

interpretationThe 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.

fundingThis work was funded by Ena Respiratory, Melbourne, Australia.

Indexed as

Virus SheddingAdministration, IntranasalAnimalsCOVID-19COVID-19 Drug TreatmentDisease Models, AnimalFemaleFerretsImmunity, InnateLipopeptidesNasal CavityPharynxReal-Time Polymerase Chain ReactionRespiratory SystemRNA, ViralSARS-CoV-2LipopeptidesRNA, ViralToll-Like Receptor 2Toll-Like Receptor 6COVID-19FerretINNA-051SARS-CoV-2TLR-2Viral shedding

Identifiers

PMID33279857
PMCPMC7711201
OpenAlexW3107221085

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.