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Toxins (Basel). 2019 Jan 10;11(1). pii: E32. doi: 10.3390/toxins11010032.

Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms.

Author information

1
CONACYT, Instituto de Biotecnología-Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, Morelos 62250, Mexico. umbarila@ibt.unam.mx.
2
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, UNAM, Apartado Postal 510-3, Cuernavaca, Morelos 62250, Mexico. ilsegmz@ibt.unam.mx.
3
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, UNAM, Apartado Postal 510-3, Cuernavaca, Morelos 62250, Mexico. lmlecan832@gmail.com.
4
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, UNAM, Apartado Postal 510-3, Cuernavaca, Morelos 62250, Mexico. timoteo@ibt.unam.mx.
5
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, UNAM, Apartado Postal 510-3, Cuernavaca, Morelos 62250, Mexico. everardoremi@gmail.com.
6
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, UNAM, Apartado Postal 510-3, Cuernavaca, Morelos 62250, Mexico. gft@ibt.unam.mx.
7
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, UNAM, Apartado Postal 510-3, Cuernavaca, Morelos 62250, Mexico. possani@ibt.unam.mx.
8
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, UNAM, Apartado Postal 510-3, Cuernavaca, Morelos 62250, Mexico. baltazar@ibt.unam.mx.

Abstract

The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy. Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity that retained recognition for its original antigen. This variant is the first antibody fragment that neutralizes the effect of an estimated 13 neurotoxins present in the venom of nine species of Mexican scorpions. This single antibody fragment showed the properties of a polyvalent antivenom. These results represent a significant advance in the development of new antivenoms against scorpion stings, since the number of components would be minimized due to their broad cross-neutralization capacity, while at the same time bypassing animal immunization.

KEYWORDS:

cross-neutralization; directed evolution; phage display; polyvalent antivenom; scFv; scorpion

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