Antivenomic of atropoides nummifer y atropoides picadoi

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RESEARCH ARTICLE

Antivenomics of Atropoides mexicanus and Atropoides picadoi snake venoms: Relationship to the neutralization of toxic and enzymatic activities
José Antúnezα, Julián Fernándezα, Bruno Lomonteα, Yamileth Anguloα, Libia Sanzα, Alicia Pérezβ, Juan José Calveteβ, José María Gutiérrezα,*
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, SanJosé, Costa Rica, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), Jaume Roig 11, 46010 Valencia, Spain
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*Correspondence to: José María Gutiérrez, Email: jose.gutierrez@ucr.ac.cr, Tel: +506 2229 3135, Fax: +506 2292 0485 Submitted: 14 July 2010; Revised: 16 August 2010; Accepted: 20 August 2010; Published: 30 September 2010

J Venom Res, 2010, Vol1, 8-17
© Copyright The Authors: This is an open access article, published under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/). This license permits non-commercial use, distribution and reproduction of the article, provided the original work is appropriately acknowledged with correct citation details.

ABSTRACT Viperidsnakes of the genus Atropoides are distributed in Mexico and Central America and, owing to their size and venom yield, are capable of provoking severe envenomings in humans. This study evaluated, using an ‘antivenomics’ approach, the ability of a polyspecific (polyvalent) antivenom manufactured in Costa Rica to recognize the proteins of Atropoides mexicanus and A. picadoi venoms, which are notincluded in the immunization mixture. In addition, the neutralization of lethal, hemorrhagic, myotoxic, coagulant, proteinase and phospholipase A2 (PLA2) activities of these venoms by the antivenom was assessed. The antivenom was highlyeffective in immunodepleting many venom components, particularly high molecular mass P-III metalloproteinases (SVMPs), L-amino acid oxidases, and some serine proteinasesand P-I SVMPs. In contrast, PLA2s, certain serine proteinases and P-I SVMPs, and a C type lectin-like protein were only partially immunodepleted, and two PLA2 molecules were not depleted at all. The antivenom was able to neutralize all toxic and enzymatic activities tested, although neutralization of lethality by A. nummifer venom was achieved when a challenge dose of 3 LD50s of venom was used,but was iffective when 4 LD50s were used. These results, and previously obtained evidence on the immunoreactivity of this antivenom towards homologous and heterologous venoms, revealed the low immunogenicity of a number of venom components (PLA2s, CRISPs, P-I SVMPs, and some serine proteinases), underscoring the need to search for innovative immunization protocols to improve the immune response tothese antigens. KEYWORDS: Atropoides picadoi, Atropoides mexicanus, antivenomics, antivenom, neutralization, toxicity, immunodepletion, snake venom
INTRODUCTION Animal-derived antivenoms constitute the cornerstone in the treatment of envenomings by snakebites worldwide (WHO, 2010). In contrast to other antibody-based immunotherapeutics, such as various antitoxins and rabies immunoglobulin, theantigens (snake venoms) used for the preparation of snake antivenoms exhibit a large intra- and inter-species variability (Chippaux et al, 1991; Alape-Girón et al, 2008; Calvete et al, 2010b). Consequently, the selection of the venoms to be used in the immunizing mixtures to raise snake antivenoms is a key issue in the design of these immunobiologicals (Gutiérrez et al, 2009a; WHO, 2010). Antivenomscan be either monospecific, if venom of only one species is used for immunization, or polyspecific, when animals are immunized with venoms from two or more species

©The Authors | Journal of Venom Research | 2010 | Vol 1 | 8-17 | OPEN ACCESS

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(Theakston et al, 2003; WHO, 2010). In either case, the generated antibodies recognize not only proteins present in the homologous venoms, but...