| abstract |
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. |