Understanding antibody-VSG interactions and early VSG expression patterns in the context of human African trypanosomiasis diagnosis

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.