According to the World Health Organization, tuberculosis is estimated to infect 13.7 million people causing active TB disease. In 2007, there were 9.3 million new cases and 1.8 million deaths caused by tuberculosis. In many countries throughout the world, the Bacillus Calmette-Guerin (BCG) vaccine is used as part of the childhood vaccination program. In the United States, where the infection rate of tuberculosis is low, the BCG vaccine is not used. The BCG vaccine is notorious for its inconsistency in preventing infection with Mycobacterium tuberculosis, and an improved vaccine has been sought by medical investigators. Researchers, lead by Dr. William Jacobs, have made new advancements in the development of an improved tuberculosis vaccine. Their research results were published online in the journal Nature Medicine. The research team used a closely related organism named Mycobacterium smegmatis in their experiments, which is normally lethal to mice. The researchers engineered a version of the Mycobacterium smegmatis which lacked key genes termed ESX-3 that are used to evade the immune system. When injected with the mutant Mycobacterium smegmatis lacking ESX-3 genes, mice were able to mount a strong immune response and survive the infection. The researchers attempted the same technique on Mycobacterium tuberculosis, but deletion of the ESX- 3 genes proved to be lethal for the Mycobacterium tuberculosis species. In an attempt to establish immunity to tuberculosis, the researchers inserted the tuberculosis ESX-3 genes into the mutant Mycobacterium smegmatis organism. Mice that were injected with this form of the bacteria were able to form immunity to Mycobacterium tuberculosis. The authors wrote, “Analysis of these adaptive immune responses indicated that the highly protective bactericidal immunity elicited by IKEPLUS was dependent on CD4+ memory T cells and involved a distinct shift in the pattern of cytokine responses by CD4+ cells. Our results establish a role for the esx-3 locus in promoting mycobacterial virulence and also identify the IKE strain as a potentially powerful candidate vaccine vector for eliciting protective immunity to M. tuberculosis”. These results are still preliminary but hopefully will form the foundation to the development of a new vaccine against Mycobacterium tuberculosis which is more effective than the current BCG vaccine.
Kari A. Sweeney et al. “A recombinant Mycobacterium smegmatis induced potent bactericidal immunity against Mycobacterium tuberculosis” Nature Medicine published online September 4, 2011 doi:10.1038/nm.2420
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