Completed Infection & Immunity Lungs & Breathing

Immune regulation of viral lung disease.

In plain English

AI plain-English summary

Every winter, thousands of infants are hospitalised with severe lung inflammation caused by respiratory syncytial virus (RSV), and no effective vaccine exists. This project tackles that gap by studying how the immune system’s regulatory T cells—the cells that normally dial down inflammation—behave during RSV infection. The researchers will run parallel experiments: detailed mechanistic studies in mice, and controlled human challenge studies where healthy adults are infected with a well-characterised strain of RSV (Memphis-37). By comparing regulatory T-cell timing, numbers, and activity in the upper airway, lungs, and blood of both species, they aim to pinpoint exactly which regulatory factors control damaging inflammation. If this works, the findings could directly inform the design of RSV vaccines that provoke protective immunity without triggering the excessive inflammation that makes infantile bronchiolitis so dangerous. The work is fundamental immunology with a clear translational target: understanding why some immune responses protect while others harm, and using that knowledge to shape vaccine design.

View original technical description
Our key goals are to perform detailed mechanistic studies of different regulatory T-cell subsets and mediators in the mouse model, run in parallel to volunteer challenge studies in man. We will define the regulatory factors involved by studying the timing, number and phenotype of regulatory T-cell subsets in the upper airway, lungs and peripheral compartments of mice. Cell transfers, depletions and the use of transgenic mice will allow precise mechanistic studies to be performed. In para llel, we will perform adult human challenge studies with a newly available well characterised inoculum (Memphis-37). Working with several key collaborators, this established but novel system will allow us to observe changes in regulatory cells and mediators in man and allow direct comparison with our murine data. We believe that this timely, ambitious but feasible proposal will lead to genuine advances in understanding the key issues in RSV disease, and therefore ultimately to the control o f inflammation in infantile bronchiolitis and the design of effective, protective vaccines.

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Researchers

Peter Openshaw (EPMC Awardee)

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Original classification

Programme Grant

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