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新型抗结核分枝杆菌疫苗成分——热休克蛋白16.3或其T细胞表位

New alternative vaccine component against mycobacterium tuberculosis--heat shock protein 16.3 or its T-cell epitope.

作者信息

Shi C, Zhang H, Zhang T, Wang X, Bai B, Zhao Y, Zhang C, Xu Z

机构信息

Lab Animal Center, Fourth Military Medical University, Shaanxi Province, China.

出版信息

Scand J Immunol. 2009 Nov;70(5):465-74. doi: 10.1111/j.1365-3083.2009.02325.x.

Abstract

Heat shock protein 16.3 (Hsp16.3) of Mycobacterium tuberculosis (MTB) containing T-cell and B-cell epitopes not only plays an important role in the survival of MTB against macrophages, but also has great potential to be used to develop new TB vaccines. In order to study whether Hsp16.3 can be replaced with its T-cell epitope for producing a vaccine against TB, we expressed and purified Hsp16.3 protein of MTB H37Rv strain and confirmed by immunoblotting. The immune responses and protection against the H37Rv induced by Hsp16.3 protein were compared with its T-cell epitope synthetic peptide in mice. The results showed that both Hsp16.3 and its synthetic peptide induced significantly stronger specific antibodies than the classical TB vaccine-BCG (bacillus Calmette-Guérin). Compared with BCG, the stimulation index in the splenolymphocyte proliferation of both recombinant protein and its synthetic peptide were remarkably enhanced, but the levels of IFN-gamma release were lower. Dramatic reduction in the numbers of MTB colony forming units (CFU) in the spleens and lungs was observed in the mice immunized with Hsp16.3 or its synthetic peptide. The protection provided by Hsp16.3 or its synthetic peptide in the lungs was equivalent to that provided by BCG. Both Hsp16.3 and its T-cell epitope are effective components and Hsp16.3 can be replaced with its T-cell epitope while developing the vaccine against TB, without requiring the complicated procedure of expressing and purifying Hsp16.3.

摘要

结核分枝杆菌(MTB)的热休克蛋白16.3(Hsp16.3)含有T细胞和B细胞表位,不仅在MTB抵抗巨噬细胞的存活中起重要作用,而且在开发新型结核病疫苗方面具有巨大潜力。为了研究Hsp16.3是否可以被其T细胞表位替代以生产抗结核病疫苗,我们表达并纯化了MTB H37Rv菌株的Hsp16.3蛋白,并通过免疫印迹进行了确认。在小鼠中比较了Hsp16.3蛋白及其T细胞表位合成肽诱导的针对H37Rv的免疫反应和保护作用。结果表明,Hsp16.3及其合成肽均诱导产生比经典结核病疫苗卡介苗(BCG)明显更强的特异性抗体。与卡介苗相比,重组蛋白及其合成肽的脾淋巴细胞增殖刺激指数均显著提高,但干扰素-γ释放水平较低。在用Hsp16.3或其合成肽免疫的小鼠中,观察到脾脏和肺部的MTB菌落形成单位(CFU)数量显著减少。Hsp16.3或其合成肽在肺部提供的保护作用与卡介苗相当。Hsp16.3及其T细胞表位都是有效的成分,在开发抗结核病疫苗时,Hsp16.3可以被其T细胞表位替代,而无需进行表达和纯化Hsp16.3的复杂程序。

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