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The "old" BCG Vaccine: | |
 | BCG (Bacillus Calmette-Guerin) is the most widely used vaccination against tuberculosis in the world. This vaccine is composed of a live, weakened strain of Mycobacterium bovis. Developed in the 1930's and it remains the only vaccination available against tuberculosis today. Unfortunately, the effectiveness of BCG in protecting infants and young children from in endemic areas from the most lethal forms of TB does not extend into their adult years. Thus, many people develop active tuberculosis later in life, even after receiving multiple doses of BCG in their first seven years. Since BCG has been used so widely and for such a long time, if it were truly effective as a long-term prophylaxis, it is unlikely that one-third of the world's population would now harbor TB infection or that two to three million people a year worldwide would die of TB, not to mention the 8 million new cases of active disease arising each year. |
Development of New Tuberculosis Vaccine Candidates: | |
 | We have hypothesized that if an attenuated M. tuberculosis strain were used as a vaccine, it might elicit a more robust immune response to challenge with M. tuberculosis than the BCG does. We further hypothesize that by deleting genes encoding immunosuppressive functions, a vaccine candidate can be made more immunogenic. To test these hypotheses, we have constructed a battery of deletion mutants of M. tuberculosis. By deleting the primary attenuating mutation of BCG, namely the RD1 region, as well as every individual genes in this region, we have demonstrated that this region encodes secreted proteins and secretion systems that export the proteins that mediating necrosis and egress of M. tuberculosis outside of lung epithelial cells and macrophages. To make the vaccine candidate safer and more immunogenic, we have also deleted the genes required for the synthesis of the vitamin pantothenate. This strain, mc26030 the result of both the RD1 deletion and the deletion of panCD genes, is significantly safer than BCG in immunocompromised mice. We are evaluating the efficacy of this strain in protecting animals against aerosol challenges with virulent M. tuberculosis. To enhance immunogenicity, we are also incorporating a number of newly-discovered mutations that inactivate immunomodulating functions of M. tuberculosis. A number of our attenuated M. tuberculosis vaccine candidate strains are undergoing rigorous testing and development in preparation for use in future "phase I" human clinical trials. |
New Vaccine Candidates: | |
For more information about this site, please contact Dr. Jordan Kriakov | |