ABSTRACT
In the last three decades, antivenom research has steadily been adopting methodologies from the field of biotechnology with the purpose of generating novel types of antivenoms with improved therapeutic benefits. In particular, recombinant DNA technology has enabled the application of monoclonal antibodies as an alternative to conventional antivenoms, which are based on polyclonal antibodies derived from the plasma of immunized animals. Scientists are now equipped to discover and engineer monoclonal antibodies of any origin, including human, which creates an avenue for developing next-generation antivenoms based on carefully defined mixtures of (human) monoclonal antibodies. Such novel antivenom products are expected to have benefits such as higher therapeutic efficacy, reduced propensity to cause adverse reactions, and possibly even lowered cost of manufacturing. However, the world has only recently seen the development of the first fully human recombinant monoclonal antibody against an animal toxin, and many methodologies that are routinely employed in other indication areas, such as oncology and autoimmune diseases, are yet to be exploited in the field of antivenom research. This creates an exciting scientific opportunity for the antivenom researcher, as the requirements that next-generation antivenoms need to be broadly neutralizing, safe to administer, cost-effective and manufacturable may bring new antibody technologies to life within envenoming therapy as well as other therapeutic areas. Advances are likely to occur within engineering of antibody cross-reactivity, design of oligoclonal antibodies, and advanced antibody manufacturing technology, which are technical areas of high importance for envenoming therapies based on recombinant (monoclonal) antibodies. In this chapter, key aspects of next-generation antivenom development are discussed, and the most promising advances in this field are presented, followed by an outlook on what the future may bring.
