synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins


Khalek, IS, Laxme, RRS, Nguyen, YTK, Khochare, S, Patel, RN, Woehl, J, Smith, JM, Saye-Francisco, K, Kim, Y, Mindrebo, LM et al (show 15 more authors) (2024) synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins Science Translational Medicine, 16 (735). eadk1867-. ISSN 1946-6234, 1946-6242

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Abstract

Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody–based universal antivenom to treat snakebite envenoming.

Item Type: Article
Uncontrolled Keywords: Animals, Humans, Mice, Snake Bites, Snake Venoms, Neurotoxins, Antivenins, Broadly Neutralizing Antibodies
Depositing User: Symplectic Admin
Date Deposited: 20 Aug 2024 15:00
Last Modified: 28 Feb 2026 01:44
DOI: 10.1126/scitranslmed.adk1867
Open Access URL: https://archive.lstmed.ac.uk/24122/
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3183951
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