Antibody development for geographically diverse hemotoxic snakebite envenoming

This PhD project aims to address the global health challenge posed by snakebite envenoming, a neglected tropical disease (NTD), responsible for high rates of mortality and morbidity worldwide. The objective is to develop broadly cross-reactive anti-hemotoxic antibodies capable of neutralizing venom from diverse geographic origins.

The research will focus on generating short chain variable fragment (scFv) libraries derived from peripheral blood lymphocytes of sheep immunized with medically important snake venoms. Using phage display and yeast surface display technologies, high affinity binders will be isolated and further engineered for enhanced efficacy and stability. The specificity and affinity of these recombinant antibodies will be valuated through enzyme-linked immunosorbent assays, flow cytometry, SDS-PAGE and surface plasmon resonance. Key research questions include assessing the capability of lead candidates to neutralize venom-induced pathology such as enzymatic and coagulation dysregulation both in vitro and in vivo. Expected findings aim to demonstrate the potential of recombinant antibodies, either alone or in combination with existing treatments (e.g. polyvalent antivenoms) as a novel therapeutic approach for snakebite envenoming.

The project addresses critical gaps in current snakebite treatment strategies, particularly the need for effective therapies against hemotoxic venoms that exhibit geographical variation in their composition and pathogenic effects. By leveraging immunological insights and recombinant technology, the study seeks to contribute towards the development of globally effective treatment for this complex and deadly NTD.