Scientists at the Max Planck Institute for Infection Biology, Berlin and at the University Clinics of Ulm have developed a putative vaccine candidate against Mycobacterium tuberculosis, the causative agent of tuberculosis. Their data have been published in the Proceedings of the National Academy of Sciences U.S.A. on April 28, 1998.
Although tuberculosis belongs to the "old" diseases, it still remains a significant global health problem. Tuberculosis is responsible for 3 million deaths annually - more than at any time-point before and more than any other infectious agent. Moreover, it has been estimated that half a billion people will suffer from tuberculosis by the year 2050. Already in 1927, a vaccine was developed which was termed bacille Calmette-Guérin (BCG) to honour the scientists who attenuated Mycobacterium bovis by more than 230 passages on bile glycerol agar. In many countries the only measure for tuberculosis control has been vaccination with BCG. General agreement exists that BCG can protect or at least ameliorate severe forms of tuberculosis in children. Yet, it seems to be of low or no protective value in adults.
M. tuberculosis belongs to the group of intracellular bacteria that replicate within the phagosomal vacuoles of resting macrophages and protection against tuberculosis depends on T cell-mediated immunity. Major histocompatiblity complex (MHC) class II-restricted CD4 T helper cells and MHC class I-restricted cytotoxic CD8 T cells are stimulated during M.tuberculosis infection, but the current BCG vaccine fails to prime CD8 T cells for tuberculosis prevention.
Over the last few years, Juergen Hess and Stefan H.E. Kaufmann from the Max Planck Institute for Infection Biology in Berlin and the University Clinics of Ulm developed recombinant ( r )- BCG strains which secrete pore-forming listeriolysin (Hly) of Listeria monocytogenes. Hly expression by r-BCG facilitates access of antigens to the cytosol of host cells which in turn represents a route for increased introduction of antigens into MHC class I presentation pathways. Their data suggest that Hly secretion endows r-BCG with an improved capacity to stimulate CD8 T cells. Because CD8 T cells play a major role in protection against M.tuberculosis infection such r-BCG strains are potential tuberculosis vaccines.
Journal
Proceedings of the National Academy of Sciences