Active Infection & Immunity Lungs & Breathing

Therapeutic immunomodulation in dengue with hyperinflammation

Funder Wellcome Charity-funded
Recipient organisation University of Oxford
Funding £1.7M
Period Aug 2022 — Jan 2027

In plain English

AI plain-English summary

Every year, up to 96 million people develop dengue, yet no drug exists to treat the infection once it turns dangerous. The problem is that severe dengue is not caused by the virus itself, but by the patient’s own immune system overreacting—triggering widespread inflammation, shock, and organ failure. This project tests whether blocking a single inflammatory signal, interleukin-1 (IL-1), can stop that cascade. The researcher will run a phase 2 clinical trial giving the drug anakinra—already used for rheumatoid arthritis—to dengue patients showing signs of hyperinflammation. Alongside the trial, they will analyse blood samples to track how the drug alters immune cell activity, cytokine levels, and genetic signatures. If IL-1 blockade works, it would provide the first targeted therapy for severe dengue, a disease that currently forces doctors to manage symptoms and wait. The mechanistic studies could also reveal which other inflammatory pathways drive the worst outcomes, pointing toward future drug combinations. This is translational medicine with a clear, immediate goal: turning a fundamental insight about immune overreaction into a practical treatment for a neglected global disease.

View original technical description
Dengue causes up to 96 million clinical infections annually. Despite this burden, there are currently no licensed therapeutics. Severe dengue is characterized by shock, organ dysfunction, cytopaenias, and vasculopathy, which occur late in the disease, during viral clearance, driven by an excessive host immune response and hypercytokinaemia. One of the most targeted ways of controlling this excessive inflammation is through interleukin-1 receptor (IL-1R) blockade (anakinra). My overarching hypothesis is IL-1 mediated pathways drive hyperinflammation and severe disease in dengue. I hypothesize that therapeutic IL-1R blockade in selected patients with dengue will improve clinical outcomes through attenuation of the inflammatory response. The accompanying immunology and transcriptomic analyses aims to reveal any additional pathophysiological pathways involved in severe dengue. I will test this hypothesis by conducting a phase 2 clinical trial of anakinra in dengue patients with hyperinflammation. I will also perform detailed mechanistic studies, investigating the effect of IL-1R blockade on dengue pathogenesis by assessing kinetics of inflammatory markers, cytokine trajectories, inflammasome and endothelial activation markers, cellular immune responses and antibody studies in trial patients with and without anakinra treatment. I will also investigate immune cell genetic signatures by disease severity and if IL-1R blockade can normalize these signatures over time.

View the original record at the funder ↗

Researchers

Sophie Yacoub (EPMC Awardee)

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Original classification

Clinical Research Career Development Fellowship

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.