Segura Álvaro, Moscoso Edwin, Umaña Deibid, Vargas Mariángela, Sánchez Andrés, Hernández Andrés, Durán Gina, Villalta Mauren, Gómez Aarón, Herrera María, Arguedas Mauricio, Gutiérrez José María, León Guillermo
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Toxicon X. 2024 Aug 30;24:100206. doi: 10.1016/j.toxcx.2024.100206. eCollection 2024 Dec.
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 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.
中东和北非（MENA）地区的蛇咬伤是一个公共卫生问题，其严重程度尚未完全明确。这些地区有几种抗蛇毒血清，但这些制剂是针对特定地理区域设计的。许多国家没有抗蛇毒血清的本地生产能力，必须获取临床性能尚未得到验证的产品。我们推测，有可能用单一的抗蛇毒血清制剂统一治疗MENA地区蝰蛇咬伤。在此，我们描述了一种针对该地区具有广泛地理覆盖范围的抗蛇毒血清（MENAVip-ICP）的设计、开发和临床前评估。我们用来自MENA地区的八种具有医学重要性的蝰蛇科蛇毒免疫马匹的血浆生产了这种抗蛇毒血清。为此，我们采用了基于两个阶段的策略：首先，用北非（NA）蛇毒免疫马匹，然后在同一批马匹上进行第二阶段免疫，使用MENA地区的蛇毒。我们从两个阶段纯化抗蛇毒血清：抗NA血清和最终产品抗MENA血清（MENAVip-ICP）。抗NA血清被视为中间制剂，其纯化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中和了同源蛇毒的致死、出血和促凝活性。与抗NA血清相比，MENAVip-ICP改善了静脉内致死率和蛇毒促凝活性的中和情况。一个值得注意的发现是，在小鼠模型中，当腹腔内注射与静脉内注射评估MENAVip-ICP时，致死率中和存在差异。在腹腔内注射时，MENAVip-ICP在中和所有蛇毒的致死率方面似乎更有效。此外，MENAVip-ICP中和了未包含在免疫方案中的MENA其他地区、中亚/东亚和撒哈拉以南非洲地区蛇种蛇毒的致死活性。我们的结果表明，MENAVip-ICP在临床前水平上中和了MENA地区蝰蛇科蛇毒诱导的主要毒性活性。因此，它是一种有前景的产品，可用于该地区蛇咬伤中毒治疗的临床评估。
