Abstract
The venom proteome of Siamese Russell’s viper from Taiwan, alongside complementary in vivo lethality neutralization assay and in vitro third-generation antivenomics assessment of the preclinical efficacy of the homologous antivenom manufactured in Taiwan CDC’s Vaccine Center, are here reported. Taiwanese Russell’s viper venom proteome comprised 25 distinct gene products, with the heterodimeric PLA2 viperotoxin-F representing the most abundant toxin (47.5% of total venom proteome). Coagulation FV-activating serine proteinase (RVV-V, 14%), the PIV-SVMP activator of FX (RVV-FX, 8.5%), and less abundant toxins from nine protein families, make up its venom proteome. Venom composition-pathology correlations of D. siamensis envenomings in Taiwan are discussed. The lethal effect of Taiwanese D. siamensis venom was 0.47 mg/g mouse. Antivenomics-guided assessment of the toxin recognition landscape of the Taiwanese Russell’s viper antivenom, in conjunction with complementary in vivo neutralization analysis, informed the antivenom’s maximal toxin immunorecognition ability (14 mg total venom proteins/vial), neutralization capacity (6.5 mg venom/vial), and relative content of lethality neutralizing antibodies (46.5% of the toxin-binding F(ab’)2 antibodies). The antivenomics analysis also revealed suboptimal aspects of the CDC-Taiwan antivenom. Strategies to improve them are suggested.
Highlights
The annual incidence of venomous snakebite in Taiwan during the period 2005–2009 was 40.49 per million persons [1]
D. siamensis (Taiwan) venom was fractionated by reverse-phase (RP) HPLC (Figure 1A) and the RP fractions analyzed by SDS-PAGE (Figure 1A, inset)
Venom proteins were separated by two-dimensional (2DE) electrophoresis (IEF/SDS-PAGE) run under non-reducing conditions in both directions and under non-reducing isoelectric focusing (IEF), followed by reduced SDS-PAGE conditions (Figure 2)
Summary
The annual incidence of venomous snakebite in Taiwan during the period 2005–2009 was 40.49 per million persons [1]. Six of the 15 species of venomous snakes found in Taiwan are responsible for most of the clinically significant envenomations in the country [2]. In relation to variation in the color pattern and symptoms of envenoming [7], identified two full species within the wide range of the Russell’s viper, Daboia russelii (South Asian Russell’s viper, west of the bay of Bengal, South Asia, including Bangladesh, India, Nepal, Pakistan and Sri Lanka) and Daboia siamensis (Siamese Russell’s viper), widely but discontinuously distributed throughout Southeast Asia, east of the Bay of Bengal, including Myanmar, Thailand, Cambodia, the Indonesian island Endeh, Flores, east Java, Komodo, and Lomblen, and southern China (Guangxi, Guangdong) and Taiwan (http://www.reptile-database.org) [8]. Lethal dose for most humans is approximately 40 to 70 mg [9]
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