Black Mamba Snake Venom Neutralized with Human Antibodies

The development of a panel of human antibodies that neutralise elements of black mamba snake toxin in an in vivo model has been described in a recent paper published in Nature Communications.

The study was a joint effort between IONTAS Limited (IONTAS), a leader in the discovery and optimisation of fully human antibodies, the Technical University of Denmark, and the Instituto Clodomiro Picado of the University of Costa Rica.

Each year, around two million people fall victim to snakebite envenoming, which leads to more than 100,000 deaths and approximately 400,000 cases of severe sequalae, such as amputation. Particularly, impoverished victims living in snake-infested areas of the tropics are at risk, and many bites are left untreated due to the unavailability of safe and effective antivenoms. Snakebite envenoming has recently been introduced on the World Health Organization’s list of neglected tropical diseases due to its high disease burden.

The “proof of concept” research described in Nature Communications identified key components, including dendrotoxins, in the black mamba’s venom which contribute to venom toxicity. Human antibodies were generated to these dendrotoxins using IONTAS Phage Display Technology and cocktails of IgG-formatted human antibodies were then shown to protect mice from dendrotoxin-mediated neurotoxicity in vivo.

Associate Professor Andreas Hougaard Laustsen, Technical University of Denmark, commented: “Current antivenoms are based on plasma-derived animal antibodies, which are effective in neutralising venom toxicity, but are also associated with serious adverse reactions, such as serum sickness, due to their non-human origin. With our work we have laid the first stone on the technological path towards the manufacture of a next-generation fully human antivenom, devoid of such drawbacks.”

Professor José María Gutiérrez, Instituto Clodomiro Picado, Universidad de Costa Rica, said: “It is rewarding to see that classic techniques in toxinology and state-of-the-art methodologies of recombinant DNA could be successfully combined to demonstrate clear therapeutic potential. This recombinant antibody approach opens the door to the development of novel tools in the treatment of snakebites.”

Dr John McCafferty, Founder and CEO, IONTAS said: “Snake envenomation is a particular burden among the world’s poorest people and the approach to treatment, based on poorly defined animal serum has not changed in decades. IONTAS were motivated to contribute our resources and experience in recombinant antibody technology towards this initial proof-of-concept study. We hope that this report will help encourage funders to support the scientific community and advance the treatment of snakebites using modern antibody engineering methods. Although many challenges remain in the development of safe, efficacious and cost-effective drug cocktails, it is an achievable goal with the ultimate reward of seeing science help improve human lives.”

This article has been republished from materials provided by IONTAS. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Laustsen, A. H., Karatt-Vellatt, A., Masters, E. W., Arias, A. S., Pus, U., Knudsen, C., . . . Mccafferty, J. (2018). In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies. Nature Communications, 9(1). doi:10.1038/s41467-018-06086-4