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Einstein researchers' prototype vaccine could provide improved protection against tuberculosis

(BRONX, NY) -- Using a novel approach, researchers at the Albert Einstein College of Medicine of Yeshiva University have developed a prototype vaccine against tuberculosis (TB) that works better in animal models than the only TB vaccine now available. In this era of multi-drug resistant TB and growing numbers of people with active TB due to coinfection with HIV, the advance could herald a needed breakthrough against one of the worlds leading killers. Their study appears in the August issue of the Journal of Clinical Investigation.

TB is caused by Mycobacterium tuberculosis, a bacterial species that infects one third of the worlds population (up to 10% of whom will develop active TB) and causes up to three million deaths annually. The only available vaccine--known as Bacille Calmette-Gurin (BCG)is a live, attenuated (weakened) strain of M. bovis, which causes TB in cattle. Despite being the worlds most widely used vaccine, BCG fails to protect adults from TB infection and doesnt reliably stem the reactivation of pulmonary TB (the most common form of the disease) in adults.

Virtually all efforts to develop a better TB vaccine have focused on boosting BCGmodifying it to elicit a stronger immune response in people, says Dr. William Jacobs, Jr., co-senior author of the paper and a Howard Hughes Medical Institute investigator at Einstein as well as professor of microbiology & immunology and molecular genetics. But we feel that tweaking the marginally useful BCG vaccine is the wrong strategy. So weve started with virulent M. tuberculosisthe organism that actually causes TB in humansand are knocking out certain genes to yield a live, attenuated M. tuberculosis strain that still produces a strong immunological response that protects people.

TB bacteria invade human cells and then--successfully evading a persons immune response--lurk inside cells and multiply. A key evasion strategy involves preventing their host cells from undergoing apopto
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Contact: Larry Katzenstein
lkatzens@aecom.yu.edu
718-430-3101
Albert Einstein College of Medicine
1-Aug-2007


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