التفاصيل البيبلوغرافية
| العنوان: |
Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins. |
| المؤلفون: |
Khalek, Irene S., Senji Laxme, R. R., Nguyen, Yen Thi Kim, Khochare, Suyog, Patel, Rohit N., Woehl, Jordan, Smith, Jessica M., Saye-Francisco, Karen, Kim, Yoojin, Misson Mindrebo, Laetitia, Tran, Quoc, Kędzior, Mateusz, Boré, Evy, Limbo, Oliver, Verma, Megan, Stanfield, Robyn L., Menzies, Stefanie K., Ainsworth, Stuart, Harrison, Robert A., Burton, Dennis R. |
| المصدر: |
Science Translational Medicine; 2/21/2024, Vol. 16 Issue 735, p1-12, 12p |
| مصطلحات موضوعية: |
SNAKE venom, NICOTINIC acetylcholine receptors, SYNTHETIC antibodies, IMMUNOGLOBULINS, SNAKEBITES |
| مستخلص: |
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. Editor's summary: Current strategies to treat snakebite envenoming rely on polyclonal antivenom derived from animals such as horses. Although these treatments can be life-saving, they can also result in serum sickness and anaphylaxis, and they require identification of the species of snake behind the bite. To address these limitations, Khalek et al. used a synthetic human antibody library to find and optimize a monoclonal antibody that could neutralize long-chain three-finger α-neurotoxins produced by the Elapidae family of snakes, which includes cobras, kraits, and mambas. The antibody was able to confer protection against envenoming in mice and functioned by mimicking the binding between the toxins and their receptors. This antibody and the approach used to find it represent a step forward on the path toward a universal, optimized antivenom. —Courtney Malo [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
