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. There is currently no specific treatment for RSV disease and identification of 'druggable' inflammatory pathways would be of great potential clinical value. Observational studies of natural infection are constrained by sampling, timing and access. The aim of INFLAMMAGE is to investigate the mechanisms of inflammation in adult volunteers using experimental human RSV infections at Imperial College London. This will enable us to investigate the RSV infection in older adult non-smokers and smokers up to 75 years of age; using in vivo and in vitro techniques, we will attempt to define novel clinical end-points and to discover pathways and biomarkers that predict outcome. This will allow us to select from a range of promising drugs in GSK's development pipeline that inhibit specific inflammatory pathways. This next phase of INFLAMMAGE will enable us to predict the possible impact of treatment with validated novel anti-inflammatory agents from GSK in human RSV disease and to discover new treatments for viral exacerbations of chronic respiratory disease, including COPD. The testing of potential drugs in disease will form the future final phase of INFLAMAGE.

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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Wiseman DJ (2020) A New Role for CXCL4 in Respiratory Syncytial Virus Disease. in American journal of respiratory and critical care medicine

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Thwaites RS (2019) The Respiratory Mucosa: Front and Center in Respiratory Syncytial Virus Disease. in American journal of respiratory and critical care medicine

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Goya S (2020) Toward unified molecular surveillance of RSV: A proposal for genotype definition. in Influenza and other respiratory viruses

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McGrath B (2020) Tracheostomy in the COVID-19 era: global and multidisciplinary guidance in The Lancet Respiratory Medicine

 
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 Senior Investigator Award
Amount £60,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2020 
End 03/2021