Innovative Immunization Strategies for Antivenom Development.

Innovative Immunization Strategies for Antivenom Development.
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DOI:
10.3390/toxins10110452
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发表时间:
2018-11-02
期刊:
影响因子:
4.2
通讯作者:
Laustsen AH
Laustsen AH
中科院分区:
医学2区
文献类型:
--
作者:
Bermúdez-Méndez E;Fuglsang-Madsen A;Føns S;Lomonte B;Gutiérrez JM;Laustsen AH

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蛇、蝎子和蜘蛛是对人类健康构成威胁的有毒动物,被这些动物咬伤或蜇伤而产生的严重中毒必须使用抗蛇毒血清治疗。目前的抗蛇毒血清基于血浆衍生的免疫球蛋白或来自高度免疫动物的免疫球蛋白片段。尽管这些药物 120 多年来一直可以挽救生命,但改进毒液治疗的机会仍然存在。在接下来的几十年中,新的生物技术工具得到应用,旨在提高抗蛇毒血清的功效、安全性和可负担性。在探索的途径中,使用合成肽表位、重组毒素(或类毒素)或 DNA 串作为免疫原的新型免疫策略已证明具有产生具有高治疗抗体效价和广泛中和能力的抗蛇毒血清的潜力。此外,这些方法避免了抗蛇毒血清生产过程中对毒液的需求,从而限制了与动物圈养和毒液收集相关的一些并发症。最后,创新免疫方法的一个重要好处是它们通常与现有的抗蛇毒血清生产装置兼容。在这篇综述中,我们汇总了所有已报道的研究,检验抗蛇毒血清开发的独立于毒液的创新免疫策略。此外,还简要描述了蛇、蝎子和蜘蛛毒液中发现的具有医学相关性的毒素家族,以及生化、生物信息学和组学工具如何帮助开发下一代抗蛇毒血清。
Snakes, scorpions, and spiders are venomous animals that pose a threat to human health, and severe envenomings from the bites or stings of these animals must be treated with antivenom. Current antivenoms are based on plasma-derived immunoglobulins or immunoglobulin fragments from hyper-immunized animals. Although these medicines have been life-saving for more than 120 years, opportunities to improve envenoming therapy exist. In the later decades, new biotechnological tools have been applied with the aim of improving the efficacy, safety, and affordability of antivenoms. Within the avenues explored, novel immunization strategies using synthetic peptide epitopes, recombinant toxins (or toxoids), or DNA strings as immunogens have demonstrated potential for generating antivenoms with high therapeutic antibody titers and broad neutralizing capacity. Furthermore, these approaches circumvent the need for venom in the production process of antivenoms, thereby limiting some of the complications associated with animal captivity and venom collection. Finally, an important benefit of innovative immunization approaches is that they are often compatible with existing antivenom manufacturing setups. In this review, we compile all reported studies examining venom-independent innovative immunization strategies for antivenom development. In addition, a brief description of toxin families of medical relevance found in snake, scorpion, and spider venoms is presented, as well as how biochemical, bioinformatic, and omics tools could aid the development of next-generation antivenoms.
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