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Handicapping tuberculosis may be the way to a better vaccine

Howard Hughes Medical Institute investigator William R. Jacobs and colleagues have produced a genetically altered strain of tuberculosis (TB) that elicits a stronger immune response than the current vaccine, bacillus Calmette-Gurin (BCG). The new vaccine improves survival of infected animals and may help put scientists on track to replace BCG, which has been used for nearly a century although it is largely ineffective.

Despite widespread vaccination programs, the World Health Organization estimates that approximately 2 billion people worldwide are infected with TB, with over 95 percent of infections occurring in developing countries. Most TB is latent, but can become active when the immune system is weak, such as during HIV infection, and more than 1.6 million die each year from this disease. In addition, resistance to current treatments is becoming increasingly common, making an effective vaccine all the more crucial.

Were very excited because this is the first vaccine strain weve ever seen that is significantly better than BCG, said Jacobs.

Jacobs worked in collaboration with Steven Porcelli at the Albert Einstein College of Medicine. The team will publish its findings in the August, 2007, issue of the Journal of Clinical Investigation.

The immune system has a very difficult time detecting and combating Mycobacterium tuberculosis, the bacteria responsible for tuberculosis. By creating a strain of TB that behaves differently, Jacobs believes he can build a vaccine that prepares the body to recognize TB when infected.

If a cell becomes aware that a pathogen has invaded, it can prevent the infection from spreading to other cells by committing cell suicidea process known as apoptosis, where the cell shuts down and is shredded into little pieces.

Immune system cells further chop up these cellular bits and present them to white blood cells called T lymphocytes. Each T lymphocyte specifically recognizes a different sma
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
1-Aug-2007


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