Standardization of anti-lethal toxin potency test of antivenoms prepared from two different Agkistrodon halys venoms

Abstract

In Korea, antivenoms for the treatment of patients bitten by venomous snakes have been imported from Japan or China. Although there is cross-reactivity between these antibodies and venoms from snakes indigenous to Korea (e.g. Agkistrodon genus), protection is not optimal. Antivenoms specifically prepared to neutralize Korean snake venoms could be more effective, with fewer side effects. To this end, we established an infrastructure to develop national standards and created a standardized method to evaluate the efficacy of two horse-derived antivenoms using mouse lethal toxin test. Additionally, we determined the antivenoms neutralizing activity against lethal doses (LD50) of Agkistrodon halys (from Japan) and Jiangzhe Agkistrodon halys (from China) venoms. We also performed cross-neutralization tests using probit analysis on each pairing of venom and antivenom in order to check the possibility of using Jiangzhe A. halys venom as a substitute for A. halys venom, the current standard. Slope of A. halys venom with A. halys antivenom was 10.2 and that of A. halys venom with Jiangzhe A. halys antivenom was 9.6. However, Slope of Jiangzhe A. halys venom with A. halys antivenom was 4.7 while that of Jiangzhe A. halys venom with Jiangzhe A. halys antivenom was 11.5. Therefore, the significant difference in slope patterns suggests that Jiangzhe A. halys venom cannot be used as a substitute for the standard venom to test the anti-lethal toxin activity of antivenoms (p<0.05)

Comparison of venom from wild and long-term captive Gloydius caucasicus and the neutralization capacity of antivenom produced in rabbits immunized with captive venom

“…Lee et al. [ 41 ] estimated the MHD of venom for samples of Agkistrodon halys from Japan and China to be 1.78 μg and 0.42 μg, respectively. Hemorrhage induced by venom may be due to a variety of hemorrhagic proteins such as snake venom metalloproteinases (SVMPs), which are abundant enzymes in venom of viperine snakes [ 42 , 43 ].…”

“…Higher doses of LCA antivenom were needed for neutralization of WA venom's lethality (5 LD50) in this study. Lee at el [ 41 ]. reported that Agkistrodon halys antivenom had anti-lethal activity against 4 LD50 of A. halys venom.…”