Tuberculosis (TB) is a major health problem and currently, the only licensed TB vaccine is
Mycobacterium bovis Bacille Calmette-Guerin (M. bovis BCG). In the present invention,
mutation of mycobacterial components reportedly involved in phagosome maturation inhibition was evaluated for vaccine purposes, as such mutations should result in better
vaccine antigen processing and presentation. Thus, BCG mutants in genes coding for ManLAM capping a-1,2-mannosyltransferases and the PI3P
phosphatase SapM were evaluated as TB vaccines in a stringent mouse model.
Vaccination with both ManLAM capping mutants and the SapM
mutant resulted in significantly longer survival as compared to non-vaccinated mice, whereas
vaccination with the parental BCG did not. Moreover, mice vaccinated with the SapM
mutant survived significantly longer than mice vaccinated with the parental BCG.; The
mutant BCG strains showed unaltered
phagocytosis, replication,
lysosome colocalization and oxidant activity in macrophages and similarly induced
autophagy in the latter. Additionally, replication and
granuloma formation in mice was unaffected, indicating BCG-equivalent safety of these vaccines.