Associated organisationsInstitut Pasteur Cambodia · Rockefeller UniversityEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£3.5M
PeriodNov 2024 — Nov 2030
In plain English
AI plain-English summary
Chikungunya virus leaves nearly half of infected patients with crippling joint pain that can last for years, yet doctors have no way to predict who will develop chronic disease or how to stop it. The problem is that the immune mechanisms driving this long-term damage remain unknown. Without understanding why some people recover fully while others suffer persistent arthritis, no effective treatments or vaccines can be developed. This project will analyse blood samples from a unique group of chikungunya patients—some who recovered, some who did not—to identify exactly which immune responses go wrong. The researchers will also use new mouse models to test how antibodies can either fight the virus or, paradoxically, fuel inflammation. If successful, this work could deliver two concrete outcomes: a biomarker test that tells patients and clinicians early on whether an infection is likely to become chronic, and a clear set of immune targets for designing vaccines or therapies that prevent long-term disease. For the millions of people living in regions where chikungunya is spreading, that would mean the difference between a temporary fever and a lifetime of painful, swollen joints.
View original technical description
Chikungunya virus (CHIKV) represents a widespread mosquito-transmitted, arthritogenic virus that causes chronic debilitating joint pain and arthritis in almost half of infected patients. Currently, no effective therapies or biomarkers predicting chronic disease exist, as the mechanisms driving chronic CHIKV symptoms remain elusive. The central hypothesis of our proposal is that dysregulated antibody responses modulate susceptibility to chronic chikungunya through impaired antiviral activity, as well as excessive and inappropriate activation of pro-inflammatory pathways. This hypothesis will be tested by the in-depth characterization of a unique cohort of chikungunya patients with resolved or chronic disease. We will comprehensively analyse the immune responses during the acute phase of CHIKV infection, aiming to identify the immune determinants of susceptibility to chronic chikungunya disease. We will additionally characterize the heterogeneity of humoral immune responses from patients with differential disease outcomes. Lastly, using novel mouse models of chikungyunya disease, we will investigate the immunopathogenic mechanisms of CHIKV infection, as well as determine the mechanisms by which antibodies modulate disease pathogenesis. These studies are expected to lead to the identification of the immune pathways and biomarkers that are associated with disease chronicity, guiding the development of novel vaccination and therapeutic strategies to prevent or treat chikungunya disease.
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