title: Assessment of the impact of solvent/detergent treatment on the quality and potency of a whole IgG equine antivenom.
abstract: We have evaluated for the first time the impact of a solvent/detergent (S/D) treatment on the quality and in vivo neutralization potency of horse-derived whole IgG antivenom used in the treatment of viperid snake bite envenoming in Central America. The S/D treatment by 1% tri (n-butyl) phosphate (TnBP) - 1% Triton X-45 at 22-25 degrees C was applied either on starting plasma or on purified immunoglobulins. The S/D agents were removed from both fractions by extractions with oil. S/D-treated plasma was subjected to caprylic acid precipitation to purify the immunoglobulins. Products were formulated, sterile-filtered, and filled into 10-mL vials, stored at 5+/-3 degrees C, and subjected to routine quality controls, SDS-PAGE, determination of anti-Bothrops asper venom antibody titre by ELISA, in vivo B. asper venom-neutralization potency tests, and safety test, comparatively with an antivenom manufactured by caprylic acid fractionation without S/D treatment. Results indicate that these conditions of S/D treatment on purified immunoglobulin yielded an antivenom of high turbidity that induced weight loss in animals. In contrast, antivenom fractionated from the S/D-treated plasma had physico-chemical and biological characteristics indistinguishable from those of the non-S/D-treated antivenom. S/D treatment of horse plasma may be considered to increase the viral safety of antivenoms.
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Segura
authors.forename: Guillermo
authors.initials: G
authors.lastname: León
authors.forename: Chen-Yao
authors.initials: CY
authors.lastname: Su
authors.forename: José-María
authors.initials: JM
authors.lastname: Gutiérrez
authors.forename: Thierry
authors.initials: T
authors.lastname: Burnouf
mesh_terms: D000465:Algorithms; D000818:Animals; D000997:Antivenins / Q000009:adverse effects / Q000187:drug effects* / Q000276:immunology / Q000627:therapeutic use; D017837:Bothrops / Q000276:immunology; D003435:Crotalid Venoms / Q000276:immunology; D003902:Detergents / Q000494:pharmacology*; D006736:Horses / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000737:chemistry / Q000187:drug effects*; D009500:Neutralization Tests / Q000379:methods* / Q000592:standards; D017830:Octoxynol / Q000494:pharmacology; D010755:Organophosphates / Q000494:pharmacology; D011786:Quality Control; D012909:Snake Bites / Q000188:drug therapy; D012997:Solvents / Q000494:pharmacology*
chemical_list: D000997:Antivenins; D003435:Crotalid Venoms; D003902:Detergents; D007074:Immunoglobulin G; D010755:Organophosphates; D012997:Solvents; D017830:Octoxynol; C009524:tributyl phosphate