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.
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