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1. 发明申请

WO2006102767A1 TUBERCULOSIS VACCINE AND METHOD FOR MAKING SAME 审中-公开
标题翻译： TUBERCULOSIS VACCINE及其制备方法
公开(公告)号：WO2006102767A1
公开(公告)日：2006-10-05
申请号：PCT/CA2006/000503
申请日：2006-04-03
申请人： McGILL UNIVERSITY , BEHR, Marcel , MOSTOWY, Serge , CHARLET, Danielle , ALEXANDER, David
发明人： BEHR, Marcel , MOSTOWY, Serge , CHARLET, Danielle , ALEXANDER, David
IPC分类号： C12N15/31 , C40B40/06 , C12Q1/68 , C12P21/02 , C12P19/34 , C07H21/00 , A61K39/04 , C12N15/74 , C12N1/21 , C07K14/35
CPC分类号： A61K39/04 , A61K2039/523 , C07K14/35
摘要： The present invention relates to an improved tuberculosis (TB) vaccine and a method for making this vaccine. The present invention further includes a method for determining the potency of TB strains. Mycobacterium bovis Bacille Calmette-Guerin (BCG) strains are genetically and phenotypically heterogeneous. Expression of the antigenic proteins MPB70 and MPB83 is known to vary considerably across BCG strains; however, the reason for this phenotypic difference has remained unknown. Because the history of BCG strain dissemination has been recorded, it has been possible to precisely determine the chronology of specific genetic changes in BCG strains (Behr and Small, 1999). A number of these mutations affect putative regulatory genes (Behr et al., 1999; Brosch et al ., 2000; Spreadbury et al ., 2005), so it was hypothesized that a mutation in a regulatory gene was likely responsible for the variable production of MPB70 and MPB83. The production of MPB70 and MPB83 across a panel of BCG strains was therefore determined, in order to assign the chronology of this phenotypic change and thereby guide studies towards identifying the responsible mutation. Interestingly, the data implicate a start codon mutation in the M. tuberculosis sigma factor K (RvO445c or sigK) and point to a highly specific link between sigK and expression of MPB70 and MPB83.
摘要翻译：本发明涉及改良的结核病（TB）疫苗和制备该疫苗的方法。本发明还包括确定TB菌株效力的方法。牛分枝杆菌Baccal Calmette-Guerin（BCG）菌株具有遗传和表型异质性。已知抗原性蛋白质MPB70和MPB83的表达在BCG菌株中显着不同; 然而，这种表型差异的原因仍然未知。由于已经记录了BCG菌株传播的历史，所以可以准确地确定BCG菌株中特定遗传变化的年表（Behr and Small，1999）。许多这些突变影响推定的调控基因（Behr等，1999; Brosch等，2000; Spreadbury等，2005），因此假设调节基因中的突变可能导致可变生产的MPB70和MPB83。因此，确定了一组BCG菌株中的MPB70和MPB83的产生，以便分配该表型变化的年表，从而指导研究来鉴定负责的突变。有趣的是，该数据涉及结核分枝杆菌s因子K（RvO445c或sigK）中的起始密码子突变，并指出sigK与MPB70和MPB83的表达之间的高度特异性连锁。

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