title: Preclinical assessment of a polyspecific antivenom against the venoms of Cerrophidion sasai, Porthidium nasutum and Porthidium ophryomegas: Insights from combined antivenomics and neutralization assays.
abstract: A polyspecific antivenom is used in Central America for the treatment of envenomings by viperid snakes. This antivenom is generated in horses hyperimmunized with a mixture of venoms from Bothrops asper, Crotalus simus and Lachesis stenophrys. The present study analyzed the ability of this antivenom to neutralize the venoms of three Central American viperid species of the 'Porthidium group', i.e. Porthidium nasutum, Porthidium ophryomegas and Cerrophidion sasai, formerly classified as Cerrophidion godmani. In addition, the immunorecognition of the components of these venoms was assessed by immunoaffinity antivenomics. The antivenom proved effective in neutralizing the lethal, hemorrhagic, myotoxic, phospholipase A(2) (PLA(2)) and proteinase activities of the three venoms, albeit exhibiting quantitative differences in the values of the Median Effective Doses (ED(50)). Excepting for certain low molecular mass bands corresponding to disintegrins, and some PLA(2)s and PI-metalloproteinases, Western blotting and immunoaffinity chromatography revealed immunorecognition of most Porthidium and Cerrophidion venom proteins. In agreement with in vivo neutralization assays, immobilized antivenom IgGs showed higher immunocapturing activity of toxins from both Porthidium taxa than from C. sasai. Overall our results demonstrate a significant paraspecific protection of the Costa Rican polyspecific antivenom against the three venoms sampled. They also stress the need to search for novel ways to enhance the immune response of horses against several weakly immunogenic venom components.
authors: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica. jose.gutierrez@ucr.ac.cr
authors: José María
authors: JM
authors: Gutiérrez
authors: Wan-Chih
authors: WC
authors: Tsai
authors: Davinia
authors: D
authors: Pla
authors: Gabriela
authors: G
authors: Solano
authors: Bruno
authors: B
authors: Lomonte
authors: Libia
authors: L
authors: Sanz
authors: Yamileth
authors: Y
authors: Angulo
authors: Juan J
authors: JJ
authors: Calvete
mesh_terms: D000818:Animals; D000997:Antivenins / Q000032:analysis / Q000276:immunology / Q000627:therapeutic use*; D002846:Chromatography, Affinity / Q000379:methods; D003435:Crotalid Venoms / Q000737:chemistry / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D006736:Horses / Q000276:immunology; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008136:Longevity / Q000187:drug effects; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D009500:Neutralization Tests; D064801:Phospholipase A2 Inhibitors; D040901:Proteomics / Q000379:methods; D012909:Snake Bites / Q000188:drug therapy / Q000276:immunology; D017819:Viperidae / Q000276:immunology / Q000378:metabolism*
chemical_list: D000997:Antivenins; D003435:Crotalid Venoms; D064801:Phospholipase A2 Inhibitors