COPD-like airway inflammation during RSV infection of older volunteers: INFLAMMAGE

Lead Research Organisation: Imperial College London
Department Name: National Heart and Lung Institute

Abstract

Based on extensive preclinical and clinical research, we hypothesise that RSV disease represents a dysregulated and over-exuberant inflammatory response to infection. Steroids have limited efficacy, and identification of druggable inflammatory pathways in severe RSV disease would be of great potential value. There are promising clinical assets ready for investigation, however, our ability to test novel therapeutics is limited by the currently available models of viral disease and clinical endpoints tied to disease processes. Observational studies of natural infection are constrained by sampling, timing and access. We therefore propose to extend the experimental human RSV infection studies established at Imperial College to investigate the pulmonary response to RSV infection in older adult non-smokers and smokers, with the development of novel clinical endpoints which can then be used to evaluate the possible impact of treatment with validated novel anti-inflammatory agents from GSK in human RSV disease and therefore in COPD.

Technical Summary

Overall, the aims of this project are to investigate the mechanisms of inflammation in older adult volunteers during respiratory viral infection in vivo and in vitro to develop novel clinical end-points and biomarkers that correlate with infection outcome. In addition to elucidating the pathways involved in steroid-resistant inflammation triggered by viral infection, the future option of treatment with a validated novel therapeutic will allow us to determine if either reducing viral-driven inflammation or directly reducing viral load improves clinical outcome. The early Parts of this project will generate data which will enable selection of an appropriate clinical therapeutic agent for investigation.

Publications

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Fraser CS (2017) Vaccines in the Prevention of Viral Pneumonia. in Clinics in chest medicine

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Marchant A (2017) Maternal immunisation: collaborating with mother nature. in The Lancet. Infectious diseases

 
Description A UK underpinning platform to study immunology and immunopathology of COVID-19:The UK Coronavirus Immunology Consortium
Amount £6,552,119 (GBP)
Funding ID MR/V028448/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2020 
End 08/2021
 
Description A first-in-human open label wild-type SARS-CoV-2 dose-finding human infection challenge study
Amount £817,899 (GBP)
Organisation Department for Business, Energy & Industrial Strategy 
Sector Public
Country United Kingdom
Start 10/2020 
End 10/2023
 
Description ISARIC - Coronavirus Clinical Characterisation Consortium (ISARIC-4C)
Amount £490,894,600 (GBP)
Funding ID MC_PC_19059 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2020 
End 09/2021
 
Description NIHR Imperial Biomedical Research Centre
Amount £90,008,747 (GBP)
Organisation Barts Health NHS Trust 
Department NIHR Biomedical Research Unit
Sector Academic/University
Country United Kingdom
Start 04/2017 
End 03/2022
 
Description Senior Investigator Award
Amount £60,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2020 
End 03/2021