The standard mouse assay of anti-venom quality does not measure antibodies neutralising the haemorrhagic activity of Vipera ammodytes venom

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• 作者：Tihana Kurtović ; ^a ; ^{tkurtovic@imz.hr} ; Adrijana Leonardi^b ; ^{adrijana.leonardi@ijs.si} ; Maja Lang Balija^a ; ^{mbalija@imz.hr} ; Marija Brgles^a ; ^{mbrgles@imz.hr} ; Lidija Habjanec^a ; Igor Križ ; aj^b ; ^{igor.krizaj@ijs.si} ; Beata Halassy^a ; ^{bhalassy@imz.hr}
• 关键词：Vipera ammodytes ; Haemorrhagin ; Ammodytoxin ; Lethal toxicity assay ; Lethal toxicity neutralisation ; Antivenom
• 刊名：Toxicon
• 出版年：2012
• 出版时间：1 June, 2012
• 年：2012
• 卷：59
• 期：7-8
• 页码：709-717
• 全文大小：454 K

文摘

The venom of Vipera ammodytes ammodytes (Vaa), like the venoms of other Viperinae snakes, is largely haemorrhagic and necrotising, and only to a lesser extent neurotoxic to humans. The components most extensively studied so far, and most probably involved in generating the observed pathologies, are haemorrhagins (H), members of the metalloproteinase group of enzymes, and neurotoxic ammodytoxins (Atxs), that belong to the secretory phospholipases A₂. Rabbit antisera were prepared containing functional antibodies specific for each class of pathology-inducing venom constituents and for both classes together. The involvement of these antibodies in neutralising the toxicity of whole Vaa venom was assessed using the ED₅₀ assay in mice. This assay is the only regulatorily approved assay for estimating anti-venom potency and as such has the task to quantify the active compound neutralising venom-induced pathology of the anti-venom. Fully functional anti-Atx antibodies were shown to be responsible for neutralising the portion of venom toxicity, while anti-H antibodies were not protective in this assay. Thus, the mouse ED₅₀ assay, intended to measure the active principle of the anti-venom, does not measure antibodies specific for Vaa venom haemorrhagins, and consequently does not fulfil its primary task from the regulatory point of view.