Research team
Understanding antibody-VSG interactions and early VSG expression patterns in the context of human African trypanosomiasis diagnosis.
Abstract
Human African trypanosomiasis (HAT), caused by Trypanosoma brucei gambiense (Tbg) parasites, is a disease prevalent in Sub-Saharan Africa. While significant progress has been made in reducing HAT cases, enhanced diagnosis is crucial for the post-elimination phase. Diagnosis relies on serological tests detecting antibodies (Abs) against variant surface glycoproteins (VSGs), specifically LiTat 1.3 and LiTat 1.5. To date, it is unclear why these VSGs are such robust diagnostic markers for gambiense-HAT (gHAT). It is thought that this is due to their predominance, meaning that it is assumed that they occur in nearly all gHAT cases during the early infection stages and induce a strong, specific Ab response. However, substantial evidence for this hypothesis is lacking. Moreover, the absence of structures for Ab-VSG complexes hampers our understanding of immune recognition. This study aims to bridge this gap by elucidating the structural features and epitopes involved in Ab-VSG interactions, focusing on the predominant gHAT VSGs. Here, the role of VSG glycosylation in Ab-VSG interactions will also be assessed. Finally, it will investigate early VSG expression patterns and validate whether predominant VSGs indeed occur early after natural transmission. The outcomes of this project will not only contribute to a fundamental understanding of trypanosome immunobiology but will also provide a molecular basis to improve gHAT diagnosis, supporting the global effort to eliminate HAT.Researcher(s)
- Promoter: Sterckx Yann
- Fellow: Danel Niki
Research team(s)
Project type(s)
- Research Project
Understanding antibody-VSG interactions and early VSG expression patterns in the context of human African trypanosomiasis diagnosis;
Abstract
Human African trypanosomiasis (HAT), caused by Trypanosoma brucei gambiense parasites, is a neglected tropical disease prevalent in Sub-Saharan Africa. While significant progress has been made in reducing HAT cases, enhanced diagnosis is crucial for the upcoming post-elimination phase. Current diagnostic methods rely on serological tests detecting antibodies (Abs) against variant surface glycoproteins (VSGs), specifically LiTat 1.3, LiTat 1.5 and (to a lesser extent) LiTat 1.6. To date, it is unclear why these VSGs are such robust diagnostic antigens for gambiense-HAT (gHAT). Their universal use is speculated to be due to their predominant character, meaning that they occur in nearly all gHAT cases during the early stages of infection and induce a strong and specific Ab response. However, substantial evidence for this hypothesis is currently lacking. The general lack of structures for Ab-VSG complexes hampers our understanding of immune recognition. This study aims to bridge this gap by elucidating the structural features and epitopes involved in Ab-VSG interactions, focusing on the predominant gHAT VSGs. Furthermore, it will investigate early VSG expression patterns and validate whether predominant VSGs indeed occur early after natural transmission. The outcomes of this project will not only contribute to a fundamental understanding of trypanosome immunobiology but also provide a molecular basis for improving gHAT diagnosis, supporting the global effort to eliminate HAT.Researcher(s)
- Promoter: Sterckx Yann
- Fellow: Danel Niki
Research team(s)
Project type(s)
- Research Project