Lim Andy Shing Seng, Tan Kae Yi, Tan Choo Hock
Venom Research and Toxicology Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
Protein and Interactomics Laboratory, Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
Acta Trop. 2024 Feb;250:107099. doi: 10.1016/j.actatropica.2023.107099. Epub 2023 Dec 12.
Snakebite envenoming (SBE) is a priority Neglected Tropical Disease listed by the World Health Organization. South Asia is heavily affected, and virtually all countries in the region import polyvalent antivenom products from India for clinical use. The imported antivenoms, however, have suboptimal effectiveness due to geographical venom variation. Recently, a domestic bivalent product, named Pakistani Viper Antivenom (PVAV) has been developed specifically for Pakistani vipers, Echis carinatus sochureki and Daboia russelii. As a bivalent viperid antivenom, it is unknown yet if PVAV exhibits higher immunological binding and neutralization activities against viper venoms from distant locales compared with polyvalent antivenoms manufactured in India. This study thus examined the preclinical efficacy of PVAV against venoms of Western Russell's Vipers and Saw-scaled Viper subspecies from selected locales in the Indian subcontinent. PVAV generally outperformed the commonly used VINS polyvalent antivenom (VPAV, manufactured in India) in binding toward venoms, and showed superior or comparable neutralization efficacy against the venom procoagulant and hemorrhagic effects of Saw-scaled Vipers as well as Russell's Vipers from Pakistan and Sri Lanka. Based on normalized potency values, PVAV is far more potent than VPAV in neutralizing the lethality of all viper venoms, except that of the Indian Russell's Viper. The study shows conserved antigenicity of toxins responsible for major toxicity across these viperid venoms, and suggests the feasible production of a viper-specific antivenom with higher potency and broader geographical utility for the region.
蛇咬伤中毒(SBE)是世界卫生组织列出的重点被忽视热带病。南亚受到严重影响,该地区几乎所有国家都从印度进口多价抗蛇毒血清产品用于临床。然而,由于地理上的毒液差异,进口的抗蛇毒血清效果欠佳。最近,一种名为巴基斯坦蝰蛇抗蛇毒血清(PVAV)的国产二价产品专门针对巴基斯坦蝰蛇——锯鳞蝰(Echis carinatus sochureki)和罗素蝰(Daboia russelii)研发。作为一种二价蝰蛇科抗蛇毒血清,与印度生产的多价抗蛇毒血清相比,PVAV对来自不同地区的蝰蛇毒液是否具有更高的免疫结合和中和活性尚不清楚。因此,本研究检测了PVAV对印度次大陆选定地区的西部罗素蝰蛇和锯鳞蝰蛇亚种毒液的临床前疗效。在与毒液的结合方面,PVAV总体上优于常用的印度生产的VINS多价抗蛇毒血清(VPAV),并且在中和锯鳞蝰蛇以及来自巴基斯坦和斯里兰卡的罗素蝰蛇毒液的促凝和出血作用方面显示出 superior 或相当的中和效果。根据标准化效价,除了印度罗素蝰蛇的毒液外,PVAV在中和所有蝰蛇毒液的致死性方面远比VPAV有效。该研究表明,这些蝰蛇科毒液中负责主要毒性的毒素具有保守的抗原性,并表明可行生产一种效力更高、地域适用性更广的蝰蛇特异性抗蛇毒血清。