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北非黑曼巴蛇和黑颈眼镜蛇种群的毒液组学和抗毒液组学特征揭示了一个潜在的重要治疗弱点。

Venomics and antivenomics profiles of North African Cerastes cerastes and C. vipera populations reveals a potentially important therapeutic weakness.

机构信息

Venoms and Toxins Laboratory, Pasteur Institute of Morocco, 1. Place Louis Pasteur, 20100-Casablanca, Morocco.

出版信息

J Proteomics. 2012 Apr 18;75(8):2442-53. doi: 10.1016/j.jprot.2012.02.021. Epub 2012 Feb 24.

DOI:10.1016/j.jprot.2012.02.021
PMID:22387316
Abstract

We report the proteomic analysis of the venom of the medically relevant snake, Cerastes cerastes, from Morocco, and the immunoreactivity profile of an experimental monospecific (CcMo_AV against Moroccan C. cerastes venom) and a commercial (Gamma-VIP against Tunisian C. cerastes and M. lebetina venoms) F(ab')(2) antivenoms towards geographic variants of C. cerastes and C. vipera venoms. The venom of C. cerastes is a low-complexity proteome composed of 25-30 toxins belonging to 6 protein families, mainly targetting the hemostatic system. This toxin arsenal explains the clinical picture observed in C. cerastes envenomings. Despite geographic compositional variation, the monospecific CcMo_AV and the Gamma-VIP divalent antivenom produced at Institut Pasteur de Tunis, showed similar immunocapturing capability towards Moroccan, Tunisian, and Egyptian C. cerastes venom proteins. Proteins partially escaping immunorecognition were all identified as PLA(2) molecules. Antivenomic analysis showed low degree of cross-reactivity of Moroccan CcMo_AV and Tunisian Gamma-VIP antivenoms towards C. vipera venom toxins. This study indicates that a more complete therapeutic cover could be achieved by including C. vipera venom in the formulation of venom immunization mixtures, thereby generating a pan-Cerastes antivenom.

摘要

我们报告了来自摩洛哥具有医学相关性的蛇 Cerastes cerastes 的毒液的蛋白质组学分析,以及一种实验性单特异性(CcMo_AV 针对摩洛哥 C. cerastes 毒液)和一种商业性(Gamma-VIP 针对突尼斯 C. cerastes 和 M. lebetina 毒液) F(ab')(2) 抗蛇毒血清对 C. cerastes 和 C. vipera 毒液地理变异体的免疫反应谱。Cerastes cerastes 的毒液是一种低复杂度的蛋白质组,由 25-30 种毒素组成,属于 6 种蛋白质家族,主要针对止血系统。这种毒素库解释了在 C. cerastes 中毒时观察到的临床症状。尽管存在地理成分的变化,但在巴斯德研究所生产的单特异性 CcMo_AV 和 Gamma-VIP 二价抗蛇毒血清对摩洛哥、突尼斯和埃及的 C. cerastes 毒液蛋白表现出相似的免疫捕获能力。部分逃避免疫识别的蛋白均被鉴定为 PLA(2)分子。抗蛇毒组学分析表明,摩洛哥的 CcMo_AV 和突尼斯的 Gamma-VIP 抗蛇毒血清对 C. vipera 毒液毒素的交叉反应程度较低。这项研究表明,通过在毒液免疫混合物的配方中加入 C. vipera 毒液,可以实现更全面的治疗覆盖,从而产生一种泛 Cerastes 抗蛇毒血清。

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