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

Khalek, Irene S. and Laxme, R. R.Senji and Nguyen, Yen Thi Kim and Khochare, Suyog and Patel, Rohit N. and Woehl, Jordan and Smith, Jessica M. and Saye-Francisco, Karen and Kim, Yoojin and Mindrebo, Laetitia Misson and Tran, Quoc and Kędzior, Mateusz and Boré, Evy and Limbo, Oliver and Verma, Megan and Stanfield, Robyn L. and Menzies, Stefanie K. and Ainsworth, Stuart and Harrison, Robert A. and Burton, Dennis R. and Sok, Devin and Wilson, Ian A. and Casewell, Nicholas R. and Sunagar, Kartik and Jardine, Joseph G. (2024) Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins. Science Translational Medicine, 16 (735): eadk1867. ISSN 1946-6234

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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.

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Journal Article
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Science Translational Medicine
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Publisher Copyright: © 2024 The Authors, some rights reserved.
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Research Output Funding/yes_externally_funded
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16 May 2024 12:20
Last Modified:
16 May 2024 12:20