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首页> 外文期刊>Infection and immunity >Surface Expression of MPT64 as a Fusion with the PE Domain of PE_PGRS33 Enhances Mycobacterium bovis BCG Protective Activity against Mycobacterium tuberculosis in Mice
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Surface Expression of MPT64 as a Fusion with the PE Domain of PE_PGRS33 Enhances Mycobacterium bovis BCG Protective Activity against Mycobacterium tuberculosis in Mice

机译：MPT64与PE_PGRS33的PE结构域融合的表面表达增强了牛分枝杆菌BCG对小鼠结核分枝杆菌的保护活性

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To improve the current vaccine against tuberculosis, a recombinant strain of Mycobacterium bovis bacillus Calmette-Guérin (rBCG) expressing a Mycobacterium tuberculosis vaccine candidate antigen (MPT64) in strong association with the mycobacterial cell wall was developed. To deliver the candidate antigen on the surface, we fused the mpt64 gene to the sequence encoding the PE domain of the PE_PGRS33 protein of M. tuberculosis (to create strain HPE-ΔMPT64-BCG), which we have previously shown to transport proteins to the bacterial surface. In a series of protection experiments in the mouse model of tuberculosis, we showed that (i) immunization of mice with HPE-ΔMPT64-BCG provides levels of protection significantly higher than those afforded by the parental BCG strain, as assessed by bacterial colonization in lungs and spleens and by lung involvement (at both 28 and 70 days postchallenge), (ii) rBCG strains expressing MPT64 provide better protection than the parental BCG strain only when this antigen is surface expressed, and (iii) the HPE-ΔMPT64-BCG-induced MPT64-specific T cell repertoire when characterized by β chain variable region-β chain joining region (BV-BJ) spectratyping indicates that protection is correlated with the ability to recruit gamma interferon (IFN-γ)-secreting T cells carrying the BV8.3-BJ1.5 (172 bp) shared rearrangement. These results demonstrate that HPE-ΔMPT64-BCG is one of the most effective new vaccines tested so far in the mouse model of tuberculosis and underscore the impact of antigen cellular localization on the induction of the specific immune response induced by rBCG.
机译：为了改进当前的抗结核疫苗，开发了一种表达与结核分枝杆菌细胞壁密切相关的表达结核分枝杆菌疫苗候选抗原（MPT64）的牛分枝杆菌卡介菌重组菌株（rBCG）。为了将候选抗原递送到表面，我们将mpt64基因融合到了编码结核分枝杆菌PE_PGRS33蛋白PE结构域的序列上（产生了HPE-ΔMPT64-BCG菌株），我们之前已经证明了该蛋白可以将蛋白转运至细菌表面。在肺结核小鼠模型的一系列保护实验中，我们显示（i）用HPE-ΔMPT64-BCG免疫小鼠所提供的保护水平明显高于亲代BCG株所提供的保护水平（通过肺部细菌定植评估） （ii）攻击后28天和70天，通过脾脏和脾脏受累，（ii）仅当该抗原表面表达时，表达MPT64的rBCG菌株才比亲本BCG菌株提供更好的保护，以及（iii）HPE-ΔMPT64-BCG- β链可变区-β链连接区（BV-BJ）谱图表征时，诱导的MPT64特异性T细胞库表明保护与募集携带BV8的分泌γ-干扰素（IFN-γ）的T细胞的能力有关。 3-BJ1.5（172 bp）共享重排。这些结果表明，HPE-ΔMPT64-BCG是迄今为止在结核病小鼠模型中测试的最有效的新疫苗之一，并强调了抗原细胞定位对诱导rBCG诱导的特异性免疫反应的影响。

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