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新型佐剂脂质-皂苷复合物的研制及其在细菌抗原实验性免疫中的应用

[Elaboration of new adjuvant lipid-saponin complex and its use at experimental immunization by bacterial antigen].

作者信息

Tsybul'skiĭ A V, Sanina N M, Li I A, Popov A M, Kostetskiĭ E Ia, Portniagina O Iu, Shnyrov V L

出版信息

Biomed Khim. 2007 May-Jun;53(3):297-306.

Abstract

Results of experiments on modification of immunostimulating complexes (ISCOM's) matrix by the replacement of the phospholipid for the glycolipid (monogalactosyldiacylglycerol) from sea macrophytes, and saponin QuillA to triterpene glycoside of cucumarioside A2-2 from Cucumaria japonica are shown. The resultant complexes include the morphological structures of two types: ISCOM-like structures with the characteristic morphology and sizes and also the tubular structures with diameter of approximately 40 nm and length of 150-400 nm. We have named these structures as TI-complexes. These TI-complexes exhibit considerably lower toxicity than ISCOM. They may include an amphiphilic protein antigen and provide immunoadjuvant effect during experimental vaccination. Under conditions of experimental immunization of mice by a weak immunogen--(subunit membrane pore protein from Y. pseudotuberculosis), TI-complexes with antigen provided stronger humoral immune response to antigen than the complexes of porin with classical ISCOM, liposomes and Freund's adjuvant. Thus, it's shown the prospect of the use of TI-complexes as a new type of adjuvant carriers for antigens.

摘要

展示了通过用来自海洋大型植物的糖脂(单半乳糖基二酰基甘油)替代磷脂以及用来自日本瓜参的葫芦素糖苷A2-2的三萜糖苷替代皂苷QuillA对免疫刺激复合物(ISCOM)基质进行修饰的实验结果。所得复合物包括两种类型的形态结构:具有特征形态和尺寸的类ISCOM结构,以及直径约40nm、长度为150 - 400nm的管状结构。我们将这些结构命名为TI复合物。这些TI复合物表现出比ISCOM低得多的毒性。它们可能包含两亲性蛋白质抗原,并在实验性疫苗接种期间提供免疫佐剂作用。在用弱免疫原(来自假结核耶尔森菌的亚单位膜孔蛋白)对小鼠进行实验性免疫的条件下,与抗原结合的TI复合物比孔蛋白与经典ISCOM、脂质体和弗氏佐剂的复合物产生更强的针对抗原的体液免疫反应。因此,展示了TI复合物作为新型抗原佐剂载体的应用前景。

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