Engineering of single-domain antibodies for next-generation snakebite antivenoms

Given the magnitude of the global snakebite crisis, strategies to ensure the quality of antivenom, as well as the availability and sustainability of its supply are under development by several research groups. Recombinant DNA technology has allowed the engineering of monoclonal antibodies and recombinant fragments as alternatives to conventional antivenoms. Besides having higher therapeutic efficacy, with broad neutralization capacity against local and systemic toxicity, novel antivenoms need to be safe and cost-effective. Due to the biological and physical chemical properties of camelid single-domain antibodies, with high volume of distribution to distal tissue, their modular format, and their versatility, their biotechnological application has grown considerably in recent decades. This article presents the most up-to-date developments concerning camelid single-domain-based antibodies against major toxins from snake venoms, the main venomous animals responsible for reported envenoming cases and related human deaths. A brief discussion on the composition, challenges, and perspectives of antivenoms is presented, as well as the road ahead for next-generation antivenoms based on single-domain antibodies.