A polygeneric immunogen composed of 22 venoms from sub-Saharan African snakes to expand the neutralization scope of the EchiTAb-plus-ICP antivenom

IF 3.6 Q2 TOXICOLOGY
Andrés Sánchez, Gina Durán, Maykel Cerdas, Jairo Gutiérrez, Álvaro Segura, María Herrera, Mariángela Vargas, Adriana Sánchez, Paola Sánchez, Gabriela Solano, Mauren Villalta, Edwin Moscoso, Deibid Umaña, Mauricio Arguedas, Aarón Gómez, José María Gutiérrez, Guillermo León
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Abstract

Recent research suggests that a polygeneric immunogen made from the venoms of the most medically important viperid and elapid snakes in sub-Saharan Africa could elicit a broader antibody response in horses compared to the current EchiTAb-plus-ICP antivenom, especially against neurotoxic elapid venoms. To test this, 25 horses that have been regularly immunized to produce this antivenom were reimmunized with an immunogen containing 22 venoms from various snake species from the genera Bitis, Echis, Dendroaspis, and both spitting and non-spitting Naja. The plasma collected from these horses was processed using the caprylic acid method to produce an industrial-scale freeze-dried antivenom. The anti-lethal neutralization scope of this new formulation was then compared to that of EchiTAb-plus-ICP which is designed to target the venoms of Bitis arietans, Echis ocellatus, Naja nigricollis, and Dendroaspis polylepis. The results indicated that adding more venoms to the immunogen did not significantly enhance the neutralization of the lethal effect of viperid venoms (except for Bitis nasicornis) or of venoms of spitting cobras (except for Naja katiensis). However, incorporating additional venoms from non-spitting neurotoxic Naja spp. and Dendroaspis spp. improved the neutralization scope of EchiTAb-plus-ICP against these neurotoxic venoms. The antivenom generated showed a wider anti-lethal neutralizing scope, as compared to the standard EchiTAb-plus-ICP antivenom and constitutes a good candidate to be tested in clinical trials in sub-Saharan Africa.

Abstract Image

由 22 种撒哈拉以南非洲蛇类毒液组成的多基因免疫原,可扩大 EchiTAb-plus-ICP 抗蛇毒血清的中和范围
最近的研究表明,与目前的EchiTAb-plus-ICP抗蛇毒血清相比,一种由撒哈拉以南非洲医学上最重要的蝰蛇和伶毒蛇毒液制成的多属免疫原可在马匹体内引起更广泛的抗体反应,尤其是针对神经毒性伶毒蛇毒液的抗体反应。为了验证这一点,用含有 22 种毒液的免疫原对 25 匹定期免疫以生产这种抗蛇毒血清的马进行了再免疫,这些毒液来自 Bitis 属、Echis 属、Dendroaspis 属以及会吐和不会吐的 Naja 属的各种蛇类。从这些马身上采集的血浆经辛酸法处理后,制成了工业规模的冻干抗蛇毒血清。然后将这种新制剂的抗致命中和范围与 EchiTAb-plus-ICP 的抗致命中和范围进行了比较,后者是针对 Bitis arietans、Echis ocellatus、Naja nigricollis 和 Dendroaspis polylepis 的毒液而设计的。结果表明,在免疫原中加入更多毒液并不能显著增强对蝰蛇毒(鼻角蝰除外)或吐毒眼镜蛇毒(卡提蛇除外)致死效应的中和作用。然而,加入了更多的非吐丝神经毒性眼镜蛇毒液后,EchiTAb-plus-ICP 对这些神经毒性毒液的中和范围得到了改善。与标准的 EchiTAb-plus-ICP 抗蛇毒血清相比,生成的抗蛇毒血清显示出更大的抗致命中和范围,是在撒哈拉以南非洲进行临床试验的理想候选物质。
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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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