Monoclonal-Based Antivenomics Reveals Conserved Neutralizing Epitopes in Type I PLA2 Molecules from Coral Snakes

For over a century, polyclonal antibodies have been used to treat snakebite envenoming and are still considered by the WHO as the only scientifically validated treatment for snakebites. Nevertheless, moderate innovations have been introduced to this immunotherapy. New strategies and approaches to un...

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Bibliographic Details
Published in:Toxins 2023-01, Vol.15 (1), p.15
Main Authors: Corrêa-Netto, Carlos, Strauch, Marcelo A., Monteiro-Machado, Marcos, Teixeira-Araújo, Ricardo, Fonseca, Juliana Guzzo, Leitão-Araújo, Moema, Machado-Alves, Maria Lúcia, Sanz, Libia, Calvete, Juan J., Melo, Paulo A., Zingali, Russolina Benedeta
Format: Article
Language:English
Subjects:
Catalytic activity
Chromatography
enzymatic activity
Enzyme-linked immunosorbent assay
Epitopes
Immunotherapy
Micrurus
Monoclonal antibodies
monoclonal antibody
myotoxicity
Neurotoxicity
Neutralization
neutralization PLA2 activity
Neutralizing
Phospholipase A2
Protein families
Proteins
Snake bites
Snakes
Toxins
Venom
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Summary:For over a century, polyclonal antibodies have been used to treat snakebite envenoming and are still considered by the WHO as the only scientifically validated treatment for snakebites. Nevertheless, moderate innovations have been introduced to this immunotherapy. New strategies and approaches to understanding how antibodies recognize and neutralize snake toxins represent a challenge for next-generation antivenoms. The neurotoxic activity of Micrurus venom is mainly due to two distinct protein families, three-finger toxins (3FTx) and phospholipases A2 (PLA2). Structural conservation among protein family members may represent an opportunity to generate neutralizing monoclonal antibodies (mAbs) against family-conserved epitopes. In this work, we sought to produce a set of monoclonal antibodies against the most toxic components of M. altirostris venom. To this end, the crude venom was fractionated, and its major toxic proteins were identified and used to generate a panel of five mAbs. The specificity of these mAbs was characterized by ELISA and antivenomics approaches. Two of the generated mAbs recognized PLA2 epitopes. They inhibited PLA2 catalytic activity and showed paraspecific neutralization against the myotoxicity from the lethal effect of Micrurus and Naja venoms’ PLA2s. Epitope conservation among venom PLA2 molecules suggests the possibility of generating pan-PLA2 neutralizing antibodies.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxins15010015