New Alternative Vaccine Component Against Mycobacterium Tuberculosis- Heat Shock Protein 16.3 or its T-Cell Epitope
New Alternative Vaccine Component Against Mycobacterium Tuberculosis- Heat Shock Protein 16.3 or its T-Cell Epitope
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DOI：
10.1111/j.1365-3083.2009.02325.x
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发表时间：
2009-11-01
影响因子：
3.7
通讯作者：
Xu, Z.
中科院分区：
文献类型：
--
作者：
Shi, C.;Zhang, H.;Xu, Z.
结核分枝杆菌（Mycobacterium tuberculosis，MTB）的热休克蛋白16.3（Heat shock protein 16.3，Hsp16.3）含有T细胞和B细胞抗原表位，不仅在结核分枝杆菌抵抗巨噬细胞的过程中发挥重要作用，而且在开发新型结核疫苗方面具有巨大的潜力。为了研究结核杆菌Hsp16.3抗原表位能否被T细胞抗原表位所取代，用于结核病疫苗的制备，我们表达并纯化了结核杆菌H37 Rv株的Hsp16.3蛋白，并通过免疫印迹进行了验证。比较了Hsp16.3蛋白及其T细胞表位合成肽诱导的小鼠免疫应答和对H37 Rv的保护作用。结果表明，Hsp16.3及其合成肽诱导的特异性抗体明显强于经典的结核疫苗BCG。与BCG相比，重组蛋白及其合成肽对脾淋巴细胞增殖的刺激指数均显著增强，但IFN-γ的释放水平较低。在用Hsp 16.3或其合成肽免疫的小鼠中观察到脾和肺中MTB菌落形成单位（CFU）的数目的急剧减少。Hsp16.3或其合成肽对肺的保护作用与BCG相当。Hsp16.3及其T细胞表位都是结核病的有效成分，在研制结核病疫苗时可以用其T细胞表位替代Hsp16.3，而不需要复杂的表达和纯化过程。
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-Guerin). 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.