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

Khalek, IS and Laxme, RRS and Nguyen, YTK and Khochare, S and Patel, RN and Woehl, J and Smith, JM and Saye-Francisco, K and Kim, Y and Mindrebo, LM and Tran, Q and K�dzior, M and Boré, E and Limbo, O and Verma, M and Stanfield, RL and Menzies, SK and Ainsworth, S and Harrison, RA and Burton, DR and Sok, D and Wilson, IA and Casewell, NR and Sunagar, K and Jardine, JG (2024) synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins. In: Science Translational Medicine, 16 (735).

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Official URL: https://doi.org/10.1126/scitranslmed.adk1867

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. © 2024 The Authors, some rights reserved.

Item Type: Journal Article
Publication: Science Translational Medicine
Publisher: American Association for the Advancement of Science
Additional Information: The copyright for this article belongs to authors.
Keywords: alpha bungarotoxin; broadly neutralizing antibody; neurotoxin; nicotinic receptor; snake venom; snake venom antiserum; broadly neutralizing antibody; neurotoxin; snake venom; venom antiserum, animal experiment; animal model; antibody library; antigenic variation; Article; binding affinity; controlled study; drug targeting; envenomation; in vitro study; inhibition kinetics; mouse; neurotoxicity; neutralization test; nonhuman; protein interaction; snake; structure analysis; animal; chemistry; human; snakebite, Animals; Antivenins; Broadly Neutralizing Antibodies; Humans; Mice; Neurotoxins; Snake Bites; Snake Venoms
Department/Centre: Division of Biological Sciences > Centre for Ecological Sciences
Date Deposited: 12 Jun 2024 06:23
Last Modified: 12 Jun 2024 06:23
URI: http://eprints.iisc.ac.in/id/eprint/84476

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