Thwarting a clever devil

Efforts to improve the TB vaccine

Bill Snyder
Published: July, 2006

Douglas Kernodle, M.D., senior research specialist Cindy Hager (right) and their colleges in Vanderbilt and the VA are now handing off the results of their labors to a non-profit foundation for development.
Photo by Dana Johnson
A Vanderbilt-led team of researchers has developed a new vaccine technology that may prevent the spread of tuberculosis, a bacterial infection that kills more than 2 million people worldwide each year.

The technology has been licensed for further product development by the non-profit Aeras Global TB Vaccine Foundation.

With support from the Bill & Melinda Gates Foundation, Aeras is working as a “product development partnership” with public and private organizations around the world. The goal is to bring an improved TB vaccine to market within the next seven to 10 years.

Mycobacterium tuberculosis can hold out in the lungs of its victims for decades, effectively “walled off” by the immune system. When immunity is compromised by diseases like AIDS, the bacterium can re-emerge in a highly contagious form that can be spread to other people through coughing.

As a result, rates of active—and highly contagious—TB are skyrocketing in developing countries, especially those with a heavy burden of AIDS, says Douglas Kernodle, M.D., the David E. Rogers Professor of Medicine at Vanderbilt University Medical Center.

The current Bacillus Calmette-Guérin (BCG) vaccine is made using a related bacterium that has been weakened or “attenuated” so it cannot cause disease. The vaccine is given annually to 100 million newborns worldwide but provides inadequate protection against the pulmonary form of TB.

In the mid-1990s, Kernodle, Kathryn Edwards, M.D., professor of Pediatrics, and their colleagues at Vanderbilt and the Veterans Affairs Medical Center in Nashville began to study superoxide dismutase, an enzyme secreted by the TB bacterium in large amounts.

The enzyme “detoxifies” oxidants (reactive oxygen species) released by certain immune cells to kill foreign invaders. The researchers believed that TB “probably evolved high-level superoxide dismutase secretion as part of its strategy for infecting human hosts,” Kernodle recalls.

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