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-Vellatt, J. Preben Morth, Anne Ljungars, Lise M. Grav, Bruno Lomonte () and Andreas H. Laustsen ()
Additional contact information
Christoffer V. Sørensen: Technical University of Denmark
Julián Fernández: Universidad de Costa Rica
Anna Christina Adams: Technical University of Denmark
Helen H. K. Wildenauer: Technical University of Denmark
Sanne Schoffelen: Technical University of Denmark
Line Ledsgaard: Technical University of Denmark
Manuela B. Pucca: Federal University of Roraima
Michael Fiebig: Absolute Antibody Ltd, Wilton Centre, Redcar
Felipe A. Cerni: University of the State of Amazonas
Tulika Tulika: Technical University of Denmark
Bjørn G. Voldborg: Technical University of Denmark
Aneesh Karatt-Vellatt: IONTAS Ltd.
J. Preben Morth: Technical University of Denmark
Anne Ljungars: Technical University of Denmark
Lise M. Grav: Technical University of Denmark
Bruno Lomonte: Universidad de Costa Rica
Andreas H. Laustsen: Technical University of Denmark

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-023-42624-5

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