Infections due to Mycobacterium tuberculosis cause over 2 million deaths/year. A major problem in combating tuberculosis is the insufficient efficacy of the current vaccine, M. bovis BCG. This is due to the fact that BCG induces, apart from protective Th1 cytokines Il-12 and IFN, also the Th2 cytokine IL-4 and the immunosuppressive cytokine IL-10. Together, this response results in subversion of an adequate protective immunity.
Current data suggest that two mycobacterial glycolipids, lipoarabinomannan (LAM) and phenolic glycolipid (PGL) play an important role in this immunosuppression. For LAM it has been proposed that especially the terminal mannose residues, the mannose cap, are responsible for its immunosuppressive activity. We will use a new strategy to overcome these known problems of inefficacy by making less immunosuppressive BCG strains that lack PGL and/or (parts of) the mannose cap.
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