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Scientists Working on New TB Vaccine - 2002-06-05


Nearly four decades since the last new tuberculosis drug and 80 years since a vaccine, several experimental compounds are in the works that researchers hope will be more effective in stemming the spread of the disease. Decoding the genome of the tuberculosis bacterium has been the key to this progress.

Tuberculosis has a dubious distinction as the world's leading infectious killer, causing two million deaths each year. The World Health Organization has said more than eight million people acquire the active form of the infection every year, and two billion people - one-third of the world's population - have dormant infection. Of these cases, 10 percent will eventually turn active.

"In my mind, it's sort of a battle and we are doing our best with existing weapons," Joon-Wook Lee said. He directs the World Health Organization's Stop TB Program. "But truly, for a major breakthrough, we need new weapons. We really need an effective vaccine and we really need effective drugs," he said.

The current 80-year-old vaccine - known by the letters BCG - is only partially effective, since it does not work in adults. No new TB drugs have appeared since 1966, and the increase in drug resistant strains of the disease is making the old ones less useful.

But researchers speaking at the World Congress on Tuberculosis in Washington say that could change, mainly because of the discovery of TB's genetic code four years ago. Biologist Douglas Young of the Imperial College School of Medicine in London says that breakthrough is allowing scientists to better understand how the TB organism behaves and gives them new targets for drugs and vaccines.

"Genome sequencing is the hard core of current biology, and TB, having spent many decades out in the wilderness as a very peripheral issue, is now very much mainstream biology. So having the genome sequence has had a big multiplier effect for us," Mr. Young said.

As a result, several companies are developing tuberculosis vaccines, according to Carol Nacy, the head of the Rockville, Maryland foundation Sequella which seeks to bring TB drug research to the market. Ms. Nacy, an immunologist, said some of the experimental vaccines seek to prevent latent TB infection from becoming active. Others are designed to enhance current drug treatments to prevent relapse. Another is a modified version of BCG and is to be tested in people by the end of this year. A different one improves the activity of the existing BCG vaccine in newborns and is due for human tests next year.

Ms. Nacy said she hopes new vaccines will help the World Health Organization meet its goal of curing 85 percent of identified tuberculosis cases by 2005, but she is cautious.

"If you're looking for the vaccine given in the usual first two years of life that lasts for 20, 30 years, we're not there yet. Moreover, I would say that we're not anywhere convinced that any of the vaccines that we're going to be testing in humans today are going to be THE vaccine, either. We simply have no way of knowing what's going to work and what's not going to work because we have no clinical experience," he said.

Drugs to cure TB are further from testing. But Douglas Young of Imperial College said researchers are working on a new generation of compounds that kill the active form of the disease while its cells multiply, as current drugs do. They are also concocting drugs to kill the bacterium while it is still latent, which today's drugs do not do. This second strategy builds upon the genome decoding, which led to discovery of an enzyme involved in the feeding of the inactive bacterium.

"So a big challenge for us is to try to identify targets in non-dividing organisms. Using molecular genetic tools, people are beginning to identify genes and enzymes that are essential not for cell division, but just for maintaining [them] even when [they] are not dividing," Mr. Young said.

This kind of drug could be important in reducing the world's massive dormant TB reservoir of two billion people. Mr. Young says it could also shorten current TB treatment regimens from six months to two. The lengthier period is now needed to kill the latent bacteria that become active and start dividing. The new drug would not have to wait for this process, and the shortened treatment time would undoubtedly increase willingness of patients to complete the regimen.

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