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 α-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.La présente invention concerne le problème sanitaire majeur que constitue la tuberculose (TB). Actuellement, le seul vaccin autorisé contre la tuberculose est le vaccin bacille Calmette-Guérin Mycobacterium bovis (BCG M. bovis). Selon la présente invention, la mutation de composants mycobactériens qui seraient impliqués dans linhibition de la maturation de phagosomes a été évaluée à des fins de vaccination, de telles mutations devant déboucher sur une amélioration en termes de traitement et de présentation dun antigène de vaccin. Ainsi, des mutants de BCG dans des gènes codant pour α-1,2-mannosyltransférases à coiffe ManLAM et la PI3P phosphatase SapM ont été évalués en tant que vaccins contre la tuberculose dans un modèle de souris stringent. La vaccination au moyen de mutants à coiffe ManLAM et du mutant SapM a e
