title: Broadening the neutralizing capacity of a family of antibody fragments against different toxins from Mexican scorpions.
abstract: New approaches aimed at neutralizing the primary toxic components present in scorpion venoms, represent a promising alternative to the use of antivenoms of equine origin in humans. New potential therapeutics developed by these approaches correspond to neutralizing antibody fragments obtained by selection and maturation processes from libraries of human origin. The high sequence identity shared among scorpion toxins is associated with an important level of cross reactivity exhibited by these antibody fragments. We have exploited the cross reactivity showed by single chain variable antibody fragments (scFvs) of human origin to re-direct the neutralizing capacity toward various other scorpion toxins. As expected, during these evolving processes several variants derived from a parental scFv exhibited the capacity to simultaneously recognize and neutralize different toxins from Centruroides scorpion venoms. A sequence analyses of the cross reacting scFvs revealed that specific mutations are responsible for broadening their neutralizing capacity. In this work, we generated a set of new scFvs that resulted from the combinatorial insertion of these point mutations. These scFvs are potential candidates to be part of a novel recombinant antivenom of human origin that could confer protection against scorpion stings. A remarkable property of one of these new scFvs (ER-5) is its capacity to neutralize at least three different toxins and its complementary capacity to neutralize the whole venom from Centruroides suffusus in combination with a second scFv (LR), which binds to a different epitope shared by Centruroides scorpion toxins.
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, Morelos, 62250, Mexico.
authors.forename: Everardo Remi
authors.initials: ER
authors.lastname: Rodríguez-Rodríguez
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, Morelos, 62250, Mexico.
authors.forename: Timoteo
authors.initials: T
authors.lastname: Olamendi-Portugal
authors.affiliation: CONACYT-Research Fellow, Laboratorio de Bioingeniería, Universidad de Colima, Km. 9 Carretera Coquimatlán-Colima, C.P. 28400, Coquimatlán, Colima, Mexico.
authors.forename: Hugo
authors.initials: H
authors.lastname: Serrano-Posada
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, Morelos, 62250, Mexico.
authors.forename: Jonathan Noé
authors.initials: JN
authors.lastname: Arredondo-López
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, Morelos, 62250, Mexico.
authors.forename: Ilse
authors.initials: I
authors.lastname: Gómez-Ramírez
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, Morelos, 62250, Mexico.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Fernández-Taboada
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, Morelos, 62250, Mexico.
authors.forename: Lourival D
authors.initials: LD
authors.lastname: Possani
authors.affiliation: Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químicas, Durango, Universidad Juárez del Estado de Durango, Av Veterinaria S/N, Circuito Universitario, CP 34120, Durango, Dgo, Mexico.
authors.forename: Gerardo Alfonso
authors.initials: GA
authors.lastname: Anguiano-Vega
authors.affiliation: CONACYT-Research Fellow, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Mexico. Electronic address: umbarila@ibt.unam.mx.
authors.forename: Lidia
authors.initials: L
authors.lastname: Riaño-Umbarila
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, Morelos, 62250, Mexico. Electronic address: baltazar@ibt.unam.mx.
authors.forename: Baltazar
authors.initials: B
authors.lastname: Becerril
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019020:Directed Molecular Evolution; D008800:Mexico; D009500:Neutralization Tests; D012604:Scorpion Venoms / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D014118:Toxins, Biological / Q000235:genetics / Q000276:immunology / Q000633:toxicity*
chemical_list: D012604:Scorpion Venoms; D014118:Toxins, Biological
keywords: Cross reactivity; Human scFvs; Phage display; Scorpion toxin neutralization