TY - JOUR
KW - General Medicine
KW - snakebite envenoming
AU - Khalek IS
AU - Senji Laxme RR
AU - Nguyen YTK
AU - Khochare S
AU - Patel RN
AU - Woehl J
AU - Smith JM
AU - Saye-Francisco K
AU - Kim Y
AU - Misson Mindrebo L
AU - Tran Q
AU - Kędzior M
AU - Boré E
AU - Limbo O
AU - Verma M
AU - Stanfield RL
AU - Menzies SK
AU - Ainsworth S
AU - Harrison RA
AU - Burton DR
AU - Sok D
AU - Wilson IA
AU - Casewell NR
AU - Sunagar K
AU - Jardine JG
AB - <p>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.</p>

BT - Science Translational Medicine
DO - 10.1126/scitranslmed.adk1867
IS - 735
LA - Eng
N2 - <p>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.</p>

PB - American Association for the Advancement of Science (AAAS)
PY - 2024
T2 - Science Translational Medicine
TI - Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins
VL - 16
SN - 1946-6234, 1946-6242
ER -