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一种联合策略,用于改进针对 spp 的珊瑚抗蛇毒血清的开发。

A Combined Strategy to Improve the Development of a Coral Antivenom Against spp.

机构信息

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, United States.

Departamento de Bioquímica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

出版信息

Front Immunol. 2019 Oct 21;10:2422. doi: 10.3389/fimmu.2019.02422. eCollection 2019.

Abstract

Accidents involving snakes are not the most common ones but are noteworthy due to their severity. Victims envenomed by snakes are at high risk of death and therefore must be treated with coral antivenom. In Brazil, the immunization mixture used to fabricate coral antivenom contains and venoms, which are difficult to be obtained in adequate amounts. Different approaches to solve the venom limitation problem have been attempted, including the use of synthetic and recombinant antigens as substitutes. The present work proposes a combined immunization protocol, using priming doses of venom and booster doses of synthetic B-cell epitopes derived from toxins (four three-finger toxins-3FTX; and one phospholipase A-PLA) to obtain coral antivenom in a rabbit model. Immunized animals elicited a humoral response against both and venoms, as detected by sera reactivity in ELISA and Western Blot. Relevant cross-reactivity of the obtained sera with other species ( venoms was also observed. The elicited antibodies were able to neutralize PLA activity of both and venoms. , immunized rabbit sera completely protected mice from a challenge with 1.5 median lethal dose (LD) of venom and 50% of mice challenged with 1.5 LD of venom. These results show that this combined protocol may be a suitable alternative to reduce the amount of venom used in coral antivenom production in Brazil.

摘要

蛇伤并不常见,但因其严重性而值得关注。被蛇咬伤的患者死亡风险很高,因此必须使用珊瑚蛇毒血清进行治疗。在巴西,用于制造珊瑚蛇毒血清的免疫混合物含有 和 毒液,这些毒液很难获得足够的数量。为了解决毒液限制问题,已经尝试了不同的方法,包括使用合成和重组抗原作为替代品。本工作提出了一种联合免疫方案,使用 毒液的初始剂量和源自 毒素的合成 B 细胞表位的加强剂量(四个三指毒素-3FTX;和一个磷脂酶 A-PLA),在兔模型中获得珊瑚蛇毒血清。免疫动物产生了针对 和 毒液的体液免疫反应,这可通过 ELISA 和 Western Blot 检测血清的反应性来证实。还观察到获得的血清与其他 种( 毒液的交叉反应性。所产生的抗体能够中和 和 毒液的 PLA 活性。 ,免疫兔血清完全保护小鼠免受 1.5 半数致死剂量(LD)的 毒液攻击,50%的小鼠受到 1.5 LD 的 毒液攻击。这些结果表明,这种联合方案可能是减少巴西珊瑚蛇毒血清生产中使用毒液量的一种合适替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/987c/6816313/3a89004a5cf2/fimmu-10-02422-g0001.jpg

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