Engineering Antivenom

Snakebite envenoming is a poverty-related infliction that has affected millions of victims worldwide, and which requires immediate international attention to improve its prevention and treatment. Currently, snakebite envenoming is treated with plasma-derived antivenoms, which are effective in neutralizing venom toxins, when adequately manufactured. However, the heterologous nature of existing antivenom products cause these to be immunogenic and therefore often associated with immunological adverse reactions in patients. A need thus exists for innovation in the field of snakebite envenoming therapy. In this dr.techn. dissertation, the different technological avenues within next-generation antivenoms are outlined and further discussed in the supporting scientific articles. The contributions of my own scientific work to antivenom research are highlighted and reviewed, focusing particularly on contributions to the field of toxicovenomics for venom analysis, recombinant expression of snake toxins, design principles behind next-generation antivenoms, discovery of broadly neutralizing human monoclonal antibodies and nanobodies using phage display technology coupled to either cross-panning or use of consensus toxins, design of high-avidity antibody formats, the use of novel antibody expression technologies, the integration of engineering and manufacturing considerations in the development of recombinant antivenoms, the use of high-throughput technology for assessment of antivenom cross-reactivity, and new pharmacology. Finally, this dissertation outlines some of the future scientific, technical, and clinical challenges that must be addressed to facilitate the development and distribution of safe and effective antivenoms at an affordable cost to impoverished snakebite victims globally.