Preclinical Evaluation of Caprylic Acid-Fractionated IgG Antivenom for the Treatment of Taipan (Oxyuranus scutellatus) Envenoming in Papua New Guinea

Abstract

Background: Snake bite is a common medical emergency in Papua New Guinea (PNG). The taipan, Oxyuranus scutellatus, inflicts a large number of bites that, in the absence of antivenom therapy, result in high mortality. Parenteral administration of antivenoms manufactured in Australia is the current treatment of choice for these envenomings. However, the price of these products is high and has increased over the last 25 years; consequently the country can no longer afford all the antivenom it needs. This situation prompted an international collaborative project aimed at generating a new, low-cost antivenom against O. scutellatus for PNG. Methodology/Principal Findings: A new monospecific equine whole IgG antivenom, obtained by caprylic acid fractionation of plasma, was prepared by immunising horses with the venom of O. scutellatus from PNG. This antivenom was compared with the currently used F(ab’)2 monospecific taipan antivenom manufactured by CSL Limited, Australia. The comparison included physicochemical properties and the preclinical assessment of the neutralisation of lethal neurotoxicity and the myotoxic, coagulant and phospholipase A2 activities of the venom of O. scutellatus from PNG. The F(ab’)2 antivenom had a higher protein concentration than whole IgG antivenom. Both antivenoms effectively neutralised, and had similar potency, against the lethal neurotoxic effect (both by intraperitoneal and intravenous routes of injection), myotoxicity, and phospholipase A2 activity of O. scutellatus venom. However, the whole IgG antivenom showed a higher potency than the F(ab’)2 antivenom in the neutralisation of the coagulant activity of O. scutellatus venom from PNG. Conclusions/Significance: The new whole IgG taipan antivenom described in this study compares favourably with the currently used F(ab’)2 antivenom, both in terms of physicochemical characteristics and neutralising potency. Therefore, it should be considered as a promising low-cost candidate for the treatment of envenomings by O. scutellatus in PNG, and is ready to be tested in clinical trials.