Discovery of human antibodies against forest cobra toxins

Snakebite envenoming is one of the world’s most neglected diseases and it constitutes a serious global health challenge in tropical regions of the world. Each year, snakebite envenoming has a death toll of 125,000 and causes 400,000 amputations. The only effective therapy is antivenom (purified IgGs from venom-immunized horses/sheep), which is often associated with severe adverse reactions to the i.v. administration of large volumes of equine/ovine IgGs. The forest cobra, N. melanoleuca, is the largest cobra species in Africa and of high medical relevance according to the World Health Organization. N. melanoleuca venom derives its toxicity from potent type I and II α-neurotoxins that target nicotinic acetylcholine receptors, causing inhibition of neuromuscular transmission. This inhibition manifests itself clinically as descending neuromuscular paralysis. Here, we report the most recent results of our ongoing work aiming at identifying human antibodies with neutralizing effects against the medically most important toxins from N. melanoleuca venom. Using phage display selection, we discovered a range of different human scFv antibodies from the IONTAS phage display library. These antibodies are currently undergoing further assessment (binding capacity and cross-reactivity to other toxins) with the aim of converting the most promising candidates into the fully human IgG format for preclinical studies. We hope that this work will help pave the way for the first recombinant snakebite antivenom based on oligoclonal mixtures of human IgG antibodies targeting medically relevant toxins from African elapid snake species.