Seattle team ready to test TB vaccine booster in humans


Oct. 14--Few Americans realize there's a vaccine against tuberculosis. It's not used here, but 120 million infants get the shot every year in parts of the world where the disease is common -- including Africa, Asia and some European countries.

The problem is, it doesn't work very well.

Called BCG (Bacille Calmette-Guerin), the vaccine provides partial protection against a virulent form of the disease, but the immunity wears off between the ages of 10 and 15.

Researchers have been searching for decades for a way to boost the vaccine and extend that protection into adulthood.

Now, Seattle scientists have developed a possible candidate to do the job.

Their new booster vaccine has been tested only in animals so far. But if the results are similar in humans, it could prove a valuable tool in reducing the toll of a disease that kills nearly 2 million people a year.

"The thing that got me excited is that this is the first example I know of where a boost strategy really made a substantial difference in outcome," said David Sherman, a tuberculosis expert at Seattle BioMed who was not involved in the project.

Scientists at the Infectious Disease Research Institute (IDRI), a nonprofit biosciences lab, have been working on the project for 15 years, said Steven Reed, the institute's founder and research director. The results were published Wednesday in the journal Science Translational Medicine.

On the same day, the World Health Organization laid out a five-year, $47 billion plan to increase testing, diagnosis and treatment of tuberculosis worldwide and boost research funding.

Tuberculosis can be treated, but the regimen includes multiple drugs and takes six months. Drug-resistant strains of the disease are becoming more common, including some that defy most weapons in the modern arsenal. With nearly a third of the world's population harboring latent or active tuberculosis infections, the disease can spread rapidly as people travel. About 120 cases turn up every year in King County, including a handful that are drug-resistant.

"If we think about making a dramatic reduction in tuberculosis death and transmission, a vaccine will be a very important component," Reed said.

In tests with guinea pigs that had received BCG injections early in their lives, the new vaccine was able to extend protection throughout the animals' life span. The sample size was small, with only eight guinea pigs getting the new vaccine. But Reed said the results, which also showed the vaccine protected mice from tuberculosis and induced a strong immune response in monkeys, are convincing enough to move into human trials.

"The real hope we have now is that we know immunity to tuberculosis can be enhanced over that provided by BCG, and it can be enhanced with an approach that is highly scalable, inexpensive and safe."

He hopes to start human trials early next year.

Even if the vaccine ultimately proves effective in people, it would probably be 10 years before it reaches the market, Reed cautioned.

Based on the preliminary results, the new vaccine is unlikely to replace BCG as a stand-alone shot, Sherman said. "Something would have to be dramatically better before the public-health infrastructure all over the world changes what it does."

As a booster, the new vaccine could be administered to children around the time they enter school, Reed believes.

Vaccine development is notoriously difficult, and animal results do not always predict what will happen in humans. But IDRI is already in discussions with two drug companies about the new vaccine, Reed said. Drug giant GlaxoSmithKline licensed an earlier, less effective version of the vaccine.

To develop the new vaccine, researchers at IDRI screened hundreds of potential target proteins from the bacterium that causes tuberculosis. They picked and combined four proteins that are important for the bug's survival, hoping for an immune response that would fight the bacteria with a four-way punch.

The research was funded by the National Institutes of Health.

As a nonprofit, IDRI's goal with any of the drugs and vaccines it develops is to license them to manufacturers -- preferably in the developing world -- so they can be provided at low cost to the people who need them, Reed said.

Sandi Doughton: 206-464-2491 or sdoughton@seattletimes.com

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