Venom protection by antibody from a snakebite hyperimmune subject

Glanville, J.; Andrade, J. C.; Bellin, M.; Kim, S.; Pletnev, S.; Tsao, D.; Verardi, R.; Bedi, R.; Friede, T.; Liao, S.; Newland, R.; Bayless, N. L.; Youssef, S.; Tully, E.; Zhang, B.; Bylund, T.; Liu, T.; Kwong, P. D.

doi:10.1101/2022.09.26.507364

bioRxiv · 10.1101/2022.09.26.507364

Venom protection by antibody from a snakebite hyperimmune subject

Glanville, J.·Andrade, J. C.·Bellin, M.·Kim, S.·Pletnev, S.·Tsao, D.·Verardi, R.·Bedi, R.·Friede, T.·Liao, S.·Newland, R.·Bayless, N. L.·Youssef, S.·Tully, E.·Zhang, B.·Bylund, T.·Liu, T.·Kwong, P. D.

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Abstract

Snake envenomation is a neglected tropical disease, causing >100,000 deaths and 300,000 permanent disabilities in humans annually. Could monoclonal antibody technology provide a solution? Here, we recover Centi-3FTX-D09, a potent broadly neutralizing antivenom antibody from the B-cell memory of a human subject with snake venom exposure. Centi-3FTX-D09 recognized a conserved neutralizing epitope on long 3-finger toxins (3FTXs), a dominant snake neurotoxin. Crystal structures of Centi-3FTX-D09 in complex with 3FTXs from mamba, taipan, krait, and cobra revealed epitope mimicry of the interface between these neurotoxins and their host target, the nicotinic acetylcholine receptor. Centi-3FTX-D09 provided in-vivo protection against diverse recombinant long 3FTXs, in-vivo rescue from whole venom challenge from cobras, black mamba, and king cobra, and, when combined with the phospholipase inhibitor varespladib, in-vivo protection extending to a majority of tested elapid venoms. Thus, a single antibody can broadly neutralize long neurotoxins and contribute to broad protection from envenomation.

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Glanville, J., Andrade, J. C., Bellin, M., Kim, S., Pletnev, S., Tsao, D., Verardi, R., Bedi, R., Friede, T., Liao, S., Newland, R., Bayless, N. L., Youssef, S., Tully, E., Zhang, B., Bylund, T., Liu, T., Kwong, P. D.. 2022-09-27. Venom protection by antibody from a snakebite hyperimmune subject. https://doi.org/10.1101/2022.09.26.507364

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