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欧洲蝰蛇毒液的免疫交叉反应性和中和作用与单特异性 Vipera berus 抗蛇毒血清 ViperaTAb 。

Immunological cross-reactivity and neutralisation of European viper venoms with the monospecific Vipera berus antivenom ViperaTAb.

机构信息

MicroPharm Limited, Station Road Industrial Estate, Newcastle Emlyn, Carmarthenshire SA38 9BY, UK.

出版信息

Toxins (Basel). 2014 Aug 19;6(8):2471-82. doi: 10.3390/toxins6082471.

Abstract

Medically important cases of snakebite in Europe are predominately caused by European vipers of the genus Vipera. The mainstay of snakebite therapy is polyclonal antibody therapy, referred to as antivenom. Here we investigate the capability of the monospecific V. berus antivenom, ViperaTAb®, to cross-react with, and neutralise lethality induced by, a variety of European vipers. Using ELISA and immunoblotting, we find that ViperaTAb® antibodies recognise and bind to the majority of toxic components found in the venoms of the Vipera species tested at comparably high levels to those observed with V. berus. Using in vivo pre-clinical efficacy studies, we demonstrate that ViperaTAb® effectively neutralises lethality induced by V. berus, V. aspis, V. ammodytes and V. latastei venoms and at much higher levels than those outlined by regulatory pharmacopoeial guidelines. Notably, venom neutralisation was found to be superior to (V. berus, V. aspis and V. latastei), or as equally effective as (V. ammodytes), the monospecific V. ammodytes "Zagreb antivenom", which has long been successfully used for treating European snake envenomings. This study suggests that ViperaTAb® may be a valuable therapeutic product for treating snakebite by a variety of European vipers found throughout the continent.

摘要

在欧洲,具有医学重要性的蛇伤病例主要是由蝰蛇属的欧洲蝮蛇引起的。蛇伤治疗的主要方法是多克隆抗体治疗,即抗蛇毒血清。在这里,我们研究了单特异性 V. berus 抗蛇毒血清 ViperaTAb®与各种欧洲蝮蛇毒液引起的致死性相互作用和中和的能力。通过 ELISA 和免疫印迹,我们发现 ViperaTAb®抗体识别并结合了在测试的 Vipera 物种毒液中发现的大多数毒性成分,其结合水平与与 V. berus 观察到的水平相当。通过体内临床前疗效研究,我们证明 ViperaTAb®能够有效地中和 V. berus、V. aspis、V. ammodytes 和 V. latastei 毒液引起的致死性,并且其中和水平远高于监管药典指南所规定的水平。值得注意的是,与单特异性 V. ammodytes“Zagreb 抗蛇毒血清”(长期以来一直成功用于治疗欧洲蛇咬伤)相比,毒液中和作用更优(V. berus、V. aspis 和 V. latastei),或与(V. ammodytes)同样有效。这项研究表明,ViperaTAb®可能是治疗整个欧洲大陆发现的各种欧洲蝮蛇咬伤的有价值的治疗产品。

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