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

doi:10.1038/s41467-023-42624-5

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

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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 language	English
Article number	173
Journal	Nature Communications
Volume	15
Number of pages	12
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-023-42624-5
Publication status	Published - 2024

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Sørensen, C. V., Fernández, J., Christina Adams, A., Wildenauer, H. H. K., Schoffelen, S., Ledsgaard, L., Pucca, M. B., Fiebig, M., Cerni, F. A., Tulika, T., Voldborg, B. G., Karatt-Vellat, A., Morth, J. P., Ljungars, A., Grav, L. M., Lomonte, B., & Laustsen, A. H. (2024). Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper. Nature Communications, 15, Article 173. https://doi.org/10.1038/s41467-023-42624-5

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title = "Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper",

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.",

author = "S{\o}rensen, {Christoffer V.} and Juli{\'a}n Fern{\'a}ndez and {Christina Adams}, Anna and Wildenauer, {Helen H. K.} and Sanne Schoffelen and Line Ledsgaard and Pucca, {Manuela B.} and Michael Fiebig and Cerni, {Felipe A.} and Tulika Tulika and Voldborg, {Bj{\o}rn G.} and Aneesh Karatt-Vellat and Morth, {J. Preben} and Anne Ljungars and Grav, {Lise M.} and Bruno Lomonte and Laustsen, {Andreas H.}",

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doi = "10.1038/s41467-023-42624-5",

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Sørensen, CV, Fernández, J, Christina Adams, A, Wildenauer, HHK, Schoffelen, S, Ledsgaard, L, Pucca, MB, Fiebig, M, Cerni, FA, Tulika, T, Voldborg, BG, Karatt-Vellat, A, Morth, JP , Ljungars, A, Grav, LM, Lomonte, B & Laustsen, AH 2024, 'Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper', Nature Communications, vol. 15, 173. https://doi.org/10.1038/s41467-023-42624-5

TY - JOUR

T1 - Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper

AU - Sørensen, Christoffer V.

AU - Fernández, Julián

AU - Christina Adams, Anna

AU - Wildenauer, Helen H. K.

AU - Schoffelen, Sanne

AU - Ledsgaard, Line

AU - Pucca, Manuela B.

AU - Fiebig, Michael

AU - Cerni, Felipe A.

AU - Tulika, Tulika

AU - Voldborg, Bjørn G.

AU - Karatt-Vellat, Aneesh

AU - Morth, J. Preben

AU - Ljungars, Anne

AU - Grav, Lise M.

AU - Lomonte, Bruno

AU - Laustsen, Andreas H.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-023-42624-5

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SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

M1 - 173

ER -

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

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