Assessment of the impact of solvent/detergent treatment on the quality and potency of a whole IgG equine antivenom.
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.
Segura
Alvaro
A
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
León
Guillermo
G
Su
Chen-Yao
CY
Gutiérrez
José-María
JM
Burnouf
Thierry
T
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*
D000997:Antivenins; D003435:Crotalid Venoms; D003902:Detergents; D007074:Immunoglobulin G; D010755:Organophosphates; D012997:Solvents; D017830:Octoxynol; C009524:tributyl phosphate