Design, development and preclinical assessment of MENAVip-ICP, a new snake antivenom with potential coverage of species in the Middle East and North Africa regions

IF 3.6 Q2 TOXICOLOGY Toxicon: X Pub Date : 2024-08-30 DOI:10.1016/j.toxcx.2024.100206
Álvaro Segura, Edwin Moscoso, Deibid Umaña, Mariángela Vargas, Andrés Sánchez, Andrés Hernández, Gina Durán, Mauren Villalta, Aarón Gómez, María Herrera, Mauricio Arguedas, José María Gutiérrez, Guillermo León
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Abstract

Snakebite in the Middle East and North Africa (MENA) is a public health problem whose magnitude is not fully known. Several antivenoms are available in these regions, but these formulations are designed for restricted geographical settings. Many countries do not have local production of antivenoms and must access products whose clinical performance has not been demonstrated. We hypothesize that it is possible to unify the treatment for viperid snakebites of MENA in a single antivenom formulation. Hereby we describe the design, development and preclinical evaluation of an antivenom of broad geographical coverage for this region (MENAVip-ICP). We produced this antivenom from the plasma of horses immunized with eight medically important venoms of viperid snake species from MENA. For this, we used a strategy based on two stages: first, immunization of horses with North African (NA) venoms, followed by a second immunization stage, on the same horses, with MENA venoms. We purified antivenoms from both stages: the Anti-NA and the final product Anti-MENA (MENAVip-ICP). Anti-NA was considered as intermediate formulation and was purified with the intention to study the progression of the immunoglobulin immune response of the horses. Antivenoms from both stages neutralized lethal, hemorrhagic, and procoagulant activities of homologous venoms. Compared to Anti-NA, MENAVip-ICP improved the neutralization profile of intravenous lethality and in vitro procoagulant activities of venoms. A notable finding was the difference in the neutralization of lethality when MENAVip-ICP was assessed intraperitoneally versus intravenously in the murine model. Intraperitoneally, MENAVip-ICP appears more effective in neutralizing the lethality of all venoms. Furthermore, MENAVip-ICP neutralized the lethal activity of venoms of species from other regions of MENA, Central/East Asia, and Sub-Saharan Africa that were not included in the immunization protocol. Our results showed that MENAVip-ICP neutralizes the main toxic activities induced by viperid MENA venoms at the preclinical level. Consequently, it is a promising product that could be clinically assessed for the treatment of snakebite envenomings in this region.

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新型蛇类抗蛇毒血清 MENAVip-ICP 的设计、开发和临床前评估,可能覆盖中东和北非地区的物种
中东和北非(MENA)的蛇咬伤是一个公共卫生问题,其严重程度尚不完全清楚。这些地区有几种抗蛇毒血清,但这些制剂是为有限的地理环境设计的。许多国家没有本地生产的抗蛇毒血清,因此必须使用临床表现尚未得到证实的产品。我们假设,可以用一种单一的抗蛇毒血清配方来统一治疗中东和北非地区的毒蛇咬伤。在此,我们介绍了一种适用于该地区广泛地域的抗蛇毒血清(MENAVip-ICP)的设计、开发和临床前评估。我们用马匹的血浆生产了这种抗蛇毒血清,马匹免疫了中东和北非地区八种在医学上具有重要意义的毒蛇毒液。为此,我们采用了一种基于两个阶段的策略:首先用北非毒液对马进行免疫,然后再用中东和北非毒液对同样的马进行第二阶段免疫。我们从这两个阶段中提纯了抗蛇毒血清:Anti-NA 和最终产品 Anti-MENA (MENAVip-ICP)。Anti-NA被视为中间配方,纯化的目的是研究马匹免疫球蛋白免疫反应的进展。两个阶段的抗蛇毒血清都能中和同种毒液的致死、出血和促凝血活性。与抗-NA相比,MENAVip-ICP改善了毒液静脉致死性和体外促凝血活性的中和状况。一个值得注意的发现是,在小鼠模型中,腹腔注射 MENAVip-ICP 与静脉注射 MENAVip-ICP 在中和致死率方面存在差异。腹腔注射 MENAVip-ICP 似乎能更有效地中和所有毒液的致死性。此外,MENAVip-ICP 还能中和免疫方案中未包括的来自中东和北非、中亚/东亚以及撒哈拉以南非洲地区的其他物种毒液的致死活性。我们的研究结果表明,MENAVip-ICP 可在临床前水平中和由中东和北非地区毒蛇毒液引起的主要毒性活动。因此,它是一种很有前景的产品,可用于临床评估,以治疗该地区的蛇咬伤。
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来源期刊
Toxicon: X
Toxicon: X Pharmacology, Toxicology and Pharmaceutics-Toxicology
CiteScore
6.50
自引率
0.00%
发文量
33
审稿时长
14 weeks
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