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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.

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