UCLA researchers have developed the first vaccine against tuberculosis that is more potent than the current commercially available vaccine, developed nearly 100 years ago.

The bacterium that causes tuberculosis - Mycobacterium tuberculosis - currently infects 2 billion people worldwide, with 8 million new cases of active tuberculosis annually. The new vaccine, tested on laboratory animals, may prove to be a better, more potent vaccine for humans.

"Tuberculosis is the greatest cause of death from a single infectious agent, killing 2 million people each year worldwide," said Marcus Horwitz, principal investigator and professor of medicine and microbiology, immunology and molecular genetics, as well as a specialist in infectious disease.

If this new vaccine proves more potent than the conventional vaccine for humans, it could have a tremendous impact, especially with the emergence of antibiotic-resistant strains. "Even a modest improvement in potency over the currently available vaccine would translate into hundreds of thousands of saved lives," Horwitz said.

While several vaccines have been tested in recent years, Horwitz said, none until now has been comparable, let alone superior, to the current, century-old vaccine, called BCG.

But the UCLA study, published in the Nov. 28 online issue of the Proceedings of the National Academy of Sciences, demonstrated that this new vaccine protects highly susceptible guinea pigs from illness following infection with Mycobacterium tuberculosis. The new vaccine was found to be 10 times more potent than commercially available BCG vaccines in an animal model. Researchers, however, caution that several years of further study will be required before the vaccine would be available to the public.

The vaccine design was based on a novel approach developed by Horwitz that uses special proteins of the bacteria to stimulate an immune response to the pathogen in the host. This new method applies to bacteria or other pathogens that cause disease by multiplying within white blood cells of the lungs and other organs. These pathogens, known as intracellular parasites, include the agents that cause tuberculosis, Legionnaires' disease and leprosy.

Horwitz reasoned that the key proteins used in a vaccine against an intracellular pathogen should not be the ones that were part of the structure of the bacterium, but the ones released by the bacterium into its environment once inside the host cell. These proteins are known as secretory proteins.

As the bacterium invades the host cell, fragments of its secretory proteins are carried to the host-cell surface and mark the infected host cell as a target for attack by the immune system. The new vaccine was designed to boost the number of fighter cells produced by the immune system that are able to recognize the markers on the infected host cell and either destroy the cell or stop the bacterium in the cell from multiplying.

To make a more potent vaccine, researchers inserted the gene encoding the major secretory protein of M. tuberculosis into two commercially available BCG vaccine strains. The resulting vaccines, known as recombinant vaccines because they contain foreign DNA, produced and released large amounts of this major secretory protein. As a result, the new vaccines were able to stimulate a particularly strong immune response to the tuberculosis bacteria.