Recent tuberculosis research holds promise for developing a more effective vaccine

Tuberculosis, a mycobacterium that infects human lungs, still claims the lives of about 2 million people every year. Existing vaccines provide questionable protection, and they can even cause disease in individuals with compromised immune systems.

But recent research at the University of Wisconsin-Madison School of Veterinary Medicine holds promise for developing a more effective vaccine.

Using new microarray technology, Adel Talaat, a microbiologist with genomics training in the veterinary school's Department of Animal Health and Biosciences, has identified the specific genes that are activated during infection with tuberculosis (TB). His work, begun during his postdoctoral training at the University of Texas Southwestern Medical Center, was published in the March 30, 2004 Proceeding of National Academy of Sciences (PNAS) journal. In the report, he compares the infection in normal mice versus mice with weak immune systems.

Knowing where and how an invader activates genes to cause disease gives scientists ammunition to develop a vaccine or drugs that can stop the disease from becoming established.

"It's like an invading army," Talaat explains. "If you know that the one thing the soldiers need to survive is potatoes, then you eliminate potatoes from the town they're invading, and the soldiers will die."

In the past, researchers could evaluate only one or two genes at a time. With the new microarray technology, developed eight years ago, they can see tens of thousands of genes at the same time. It's a fluorescence-based technology that in effect "lights up" gene activity so that computers can track and evaluate the expression levels of genes that establish infection.

According to Talaat, the old methods were a random process, like searching for a needle in a haystack. The sheer volume of data available through the new technology makes progress much more rapid and systematic. Because of the volume possible, Talaat has been able to provide a complete overview of the TB disease process. He has identified all the genes that the TB pathogens activate at all stages of the infection. Armed with this complete knowledge, scientists can now develop a much more targeted and effective vaccine.

"It's easy to study an infectious agent in a flask," Talaat says. "But that doesn't tell you what happens during an infection."

Understanding how the disease and host interact is key to developing a combative strategy, and that is what the microarray studies have provided.

The next step is to develop vaccines based on the knowledge gained. Once vaccines have been found effective in at least two animal models, human clinical trials can begin.