Protection against murine tuberculosis by an attenuated recombinant Salmonella typhimurium vaccine strain that secretes the 30-kDa antigen of Mycobacterium bovis BCG

A recombinant (r-) Salmonella typhimurium aroA vaccine that secretes the na turally secreted protein of Mycobacterium bovis strain BCG, Ag85B, by means of the HlyB/HlyD/TolC export machinery (termed p30 in the following) was c onstructed. In contrast to r-S. typhimurium control, oral vaccination of mi ce with the r-S. typhimurium p30 construct induced partial protection again st an intravenous challenge with the intracellular pathogen Mycobacterium t uberculosis, resulting in similar vaccine efficacy comparable to that of th e systemically administered attenuated M. bovis BCG strain. The immune resp onse induced by r-S. typhimurium p30 was accompanied by augmented interfero n-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) levels prod uced by restimulated splenocytes. These data suggest that the HlyB/ HlyD/To lC-based antigen delivery system with attenuated r-S, typhimurium as carrie r is capable of inducing an immune response against mycobacterial antigens. (C) 2000 Federation of European Microbiological Societies. Published by El sevier Science B.V. All rights reserved.