Identification of antigens specific to non-tuberculous mycobacteria: the Mce family of proteins as a target of T cell immune responses.

Identification of antigens specific to non-tuberculous mycobacteria: the Mce family of proteins as a target of T cell immune responses.
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DOI:
10.1371/journal.pone.0026434
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
McShane H
McShane H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Checkley AM;Wyllie DH;Scriba TJ;Golubchik T;Hill AV;Hanekom WA;McShane H

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缺乏有效的结核病疫苗阻碍了当前抗击结核病大流行的努力。关于卡介苗为何在热带国家保护性较差的一种理论是,接触非结核分枝杆菌 (NTM) 会降低卡介苗的功效。目前有几种新的结核病疫苗正在进行临床试验,NTM 暴露也可能与此有关。在没有特定抗原的情况下,无法准确评估 NTM 暴露;已知存在于 NTM 中但不存在于结核分枝杆菌和 BCG 中的那些。因此,我们使用生物信息学流程来定义常见 NTM 中存在而结核分枝杆菌复合体中不存在的蛋白质,使用蛋白质 BLAST、TBLASTN 和短序列蛋白质 BLAST 来确保该过程的特异性。然后,我们评估了健康的南非人以及有记录暴露于 NTM 的英国和美国患者对这些蛋白质的免疫反应。使用离体 ELISpot 和 6 天增殖测定,检测到来自哺乳动物细胞进入家族的一组蛋白质和一组假设蛋白质的低水平反应。这些早期发现可能为在人群水平上描述 NTM 暴露特征提供基础,这在结核病疫苗设计领域以及诊断测试的开发中都有应用。
The lack of an effective TB vaccine hinders current efforts in combating the TB pandemic. One theory as to why BCG is less protective in tropical countries is that exposure to non-tuberculous mycobacteria (NTM) reduces BCG efficacy. There are currently several new TB vaccines in clinical trials, and NTM exposure may also be relevant in this context. NTM exposure cannot be accurately evaluated in the absence of specific antigens; those which are known to be present in NTM and absent from M. tuberculosis and BCG. We therefore used a bioinformatic pipeline to define proteins which are present in common NTM and absent from the M. tuberculosis complex, using protein BLAST, TBLASTN and a short sequence protein BLAST to ensure the specificity of this process. We then assessed immune responses to these proteins, in healthy South Africans and in patients from the United Kingdom and United States with documented exposure to NTM. Low level responses were detected to a cluster of proteins from the mammalian cell entry family, and to a cluster of hypothetical proteins, using ex vivo ELISpot and a 6 day proliferation assay. These early findings may provide a basis for characterising exposure to NTM at a population level, which has applications in the field of TB vaccine design as well as in the development of diagnostic tests.
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