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TB Gene Tweak Could Bring Better Vaccines

WEDNESDAY Aug. 1, 2007 -- Removing a key gene from the tuberculosis bacterium may lead to a more effective TB vaccine than the current shot, called Bacille Calmette-Guerin (BCG), new research suggests.

"Virtually all efforts to develop a better TB vaccine have focused on boosting BCG -- modifying it to elicit a stronger immune response in people," study co-senior author Dr. William Jacobs Jr., of Albert Einstein College of Medicine, New York City, said in a prepared statement. "But we feel that tweaking the marginally useful BCG vaccine is the wrong strategy."

Instead, Jacobs said, "we've started with virulent Mycobacterium tuberculosis, the organism that actually causes TB in humans, and are knocking out certain genes to yield a live, attenuated M. tuberculosis strain that still produces a strong immunological response that protects people."

TB, caused by M. tuberculosis, leads to three million deaths annually worldwide. The bacterium invades cells and then multiplies. Occasionally, invaded cells will die rather than multiply, exposing the tuberculosis bacteria to attacks from T-cells, key components of the body's immune system.

Researchers at the Albert Einstein College of Medicine of Yeshiva University located a gene called secA2 on M. tuberculosis that prevents the host cell from committing suicide. By removing the gene, the researchers gave cells an edge over the tuberculosis bacterium, potentially forging the way for future vaccine research.

BCG is the only currently available vaccine and is generally thought not to provide adequate long-term protection. It is a live, weakened strain of M. bovis, which causes TB in cattle.

Writing in the August issue of the Journal of Clinical Investigation, the researchers confirmed that when they injected the genetically altered strain of M. tuberculosis into mammalian cells, the cells were able to self-destruct, eliciting a strong and long-lasting T-cell response against the bacteria. The researchers estimated that human clinical trials for the vaccine could begin within three years.

"Our secA2 mutant TB vaccine elicited protective immunity that was measurably superior to the standard BCG vaccine," senior author Dr. Steven Porcelli said in a prepared statement. "Two months after vaccination, significantly fewer bacteria persisted in the tissues of secA2 mutant-vaccinated animals than in the tissues of animals vaccinated with BCG. And compared with BCG, animals vaccinated with the mutant vaccine had much larger populations of the vital CD8+ memory T-cells that a vaccine must elicit to optimally protect against infection."

More information

For an overview of tuberculosis, visit the U.S. Centers for Disease Control and Prevention.

Posted: August 2007


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