Contributions of the snake venoms of Bothrops asper , Crotalus simus and Lachesis stenophrys to the paraspecificity of the Central American polyspecific antivenom (PoliVal-ICP) Gabriela Solano, Aar  on G  omez, Greivin Corrales, Danilo Chac  on, Ricardo Estrada, Guillermo Le  on * Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San Jos e, Costa Rica article info Article history: Received 16 November 2017 Received in revised form 22 January 2018 Accepted 24 January 2018 Available online 4 February 2018 Keywords: Antivenom Bothrops asper Crotalus simus Lachesis stenophrys Paraspecificity abstract PoliVal-ICP antivenom is produced from plasma of horses immunized toward the venoms of Bothrops asper, Crotalus simus and Lachesis stenophrys. The antibody response induced by these venoms confers PoliVal-ICP the capacity to neutralize the venoms of the most important Central American viperids, including not only homologous venoms (i.e., venoms used as immunogen), but many heterologous venoms (i.e., venoms not used as immunogen). In this work, the individual contributions of homologous venoms to the paraspecificity of PoliVal-ICP were inferred from the capacity of experimental mono- specific antivenoms toward venoms of B. asper (anti-Ba), C. simus (anti-Cs) and L. stenophrys (anti-Ls), and an experimental polyspecific antivenom (anti-Ba/Cs/Ls) to neutralize the lethality induced by different venoms in mice. It was found that all antivenoms neutralized their corresponding homologous venoms. Moreover, the anti-Ba antivenom cross-neutralized the venoms of Agkistrodon howardgloydi, Atropoides picadoi, Bothriechis lateralis, Bothriechis supraciliaris and Porthidium ophryomegas; the anti-Cs antivenom cross-neutralized the venoms of B. lateralis, B. supraciliaris, Cerrophidion sasai and Porthidium nasutum; and the anti-Ls antivenom cross-neutralized the venoms of B. lateralis, B. supraciliaris, C. sasai and Lachesis melanocephala. All venoms neutralized by any monospecific antivenom were also neutralized by the anti-Ba/Cs/Ls antivenom. Venoms of Atropoides mexicanus, Bothriechis nigroviridis and Bothriechis schlegelii were not neutralized by any experimental antivenom, thus explaining the limitations of PoliVal- ICP to neutralize these venoms. Consequently, an enlargement of the neutralization scope of PoliVal-ICP could be achieved by including these venoms in the group of those used as immunogens. © 2018 Elsevier Ltd. All rights reserved. 1. Introduction The Central American herpetofauna includes around 32 species of viperids (Pyron et al., 2013; www.reptile-database.com), which may cause morbidity, disability, and death (WHO, 2016). Among these species, Bothrops asper and Crotalus simus are considered of greatest medical importance in the region by the World Health Organization (WHO) since they have been identified as responsible of most of the 5500 snakebite envenomations that are reported each year (Guti errez, 2014). The composition of the venoms of Central American viperids includes several types of toxins, mainly Zn 2þ -dependent metalloproteinases (SVMPs), phospholipases A 2 (PLA 2 s), serine proteinases (SVSPs) and L-aminoacid oxidases (LAAOs). Other types of toxins such as disintegrins (DIS), C-type lectins/lectin-like pro- teins (CTL), cysteine-rich secretory proteins (CRISPs), nerve growth factors (NGFs), vascular endothelial growth factors (VEGFs), 5 0 - nucleotidases (NUCL), phosphodiesterases (PDE), Kazal-type pro- teins (KAZ) and three-finger toxins (3FTxs) have also been found in these venoms, but in lower concentrations (Lomonte et al., 2014a). Each type or toxins confers snake venoms the capacity to pro- duce particular toxic effects (i.e., edema, necrosis, local/systemic hemorrhage, coagulopathy, neurotoxicity and lethality). As the relative abundance and activity of the different types of toxins change from one species to another, venoms of different snakes have different toxicity profile (Russell et al., 1997; Guti errez et al., 2014). Even so, the clinical pictures of envenomations produced by different viperids are similar and that hinders the diagnosis of * Corresponding author. E-mail address: guillermo.leon@ucr.ac.cr (G. Le on). Contents lists available at ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon https://doi.org/10.1016/j.toxicon.2018.01.016 0041-0101/© 2018 Elsevier Ltd. All rights reserved. Toxicon 144 (2018) 1e6