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

机译:鉴定非结核分枝杆菌特有的抗原:Mce蛋白家族是T细胞免疫反应的靶标。

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摘要

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.
机译: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。关于为什么卡介苗在热带国家保护性较低的一种理论是,接触非结核分枝杆菌(NTM)会降低卡介苗的功效。当前有几种新的结核病疫苗正在临床试验中,在这种情况下,NTM暴露也可能是相关的。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中且结核分枝杆菌和BCG中不存在的那些因此,我们使用生物信息学流水线来定义存在于普通NTM中且不存在于结核分枝杆菌复合体中的蛋白质,并使用蛋白质BLAST,TBLASTN和短序列蛋白质BLAST来确保该过程的特异性。然后,我们在健康的南非人以及来自英国和美国的患者中评估了对这些蛋白质的免疫反应,并记录了他们对NTM的暴露。使用离体ELISpot和6天增殖试验,检测到对来自哺乳动物细胞进入家族的蛋白质簇和假设的蛋白质簇的低水平反应。这些早期发现可能为表征人群中NTM的暴露提供基础,这在结核病疫苗设计以及诊断测试的开发中具有应用。

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