Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper

Christoffer V. Sørensen, Julián Fernández, Anna Christina Adams, Helen H. K. Wildenauer, Sanne Schoffelen, Line Ledsgaard, Manuela B. Pucca, Michael Fiebig, Felipe A. Cerni, Tulika Tulika, Bjørn G. Voldborg, Aneesh Karatt-Vellat, J. Preben Morth, Anne Ljungars, Lise M. Grav, Bruno Lomonte*, Andreas H. Laustsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Improved therapies are needed against snakebite envenoming, which kills and permanently disables thousands of people each year. Recently developed neutralizing monoclonal antibodies against several snake toxins have shown promise in preclinical rodent models. Here, we use phage display technology to discover a human monoclonal antibody and show that this antibody causes antibody-dependent enhancement of toxicity (ADET) of myotoxin II from the venomous pit viper, Bothrops asper, in a mouse model of envenoming that mimics a snakebite. While clinical ADET related to snake venom has not yet been reported in humans, this report of ADET of a toxin from the animal kingdom highlights the necessity of assessing even well-known antibody formats in representative preclinical models to evaluate their therapeutic utility against toxins or venoms. This is essential to avoid potential deleterious effects as exemplified in the present study.
Original languageEnglish
Article number173
JournalNature Communications
Volume15
Number of pages12
ISSN2041-1723
DOIs
Publication statusPublished - 2024

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