Part A – AI-Designed Protein Binders Tackle a Century-Old Challenge: Tc24 as a Universal Vaccine Antigen for Chagas Disease Part B – Expression, Purification and Biophysical Characterisation of de novo binders designed against the Flagellar Calcium Binding Protein, Tc24
Abstract
Part A – Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains one of the most neglected tropical diseases, disproportionately affecting low-income, rural populations across Latin America. Despite over a century since its discovery, there is still no effective vaccine and therapies currently rely on the usage of nifurtimox and benznidazole, which have been linked to severe side effects. This review explores the multifaceted challenges of developing both a therapeutic and prophylactic treatment for Chagas disease. Particular attention is given to the flagellar calcium-binding protein Tc24, a highly conserved, immunogen expressed across all morphological stages of T. cruzi. In parallel, this review examines how artificial intelligence (AI) and deep learning (DL) platforms are revolutionising structural prediction and binder design. These technologies enable the in silico development of both high-affinity and target-specific binders at low cost. In summary, this review proposes the integration of conserved antigen targets, with AI-guided binder design presents a novel framework for overcoming current barriers in vaccine development, offering renewed hope for the prevention and management of Chagas disease. Part B – Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains one of the most neglected tropical diseases, disproportionately effecting affecting socioeconomically impoverished regions across Latin America. Despite over a century…
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