Outwitting TB: enhanced vaccine protects mice in lab tests.

The best vaccine against tuberculosis is also the only vaccine against tuberculosis, and it's not a great one at that. Called BCG, it protects many children, but it fails miserably in shielding adults.

By genetically modifying the weakened bacterium that makes up BCG, European scientists working with mice have developed a vaccine that seems to offer better protection than BCG does. They report their work in the Sept. 1 Journal of Clinical Investigation.

BCG is shorthand for bacille Calmette-Guerin, the bacterium that bears the names of the two scientists who created the vaccine by weakening a strain of cattle tuberculosis in 1921. The advent of antibiotics since then has largely enabled industrialized countries to control TB without the vaccine. But BCG is widely used in developing countries: 3 billion people have received it.

Nevertheless, 8 million new TB cases arise each year, including many that are resistant to common antibiotics, according to National Institutes of Health statistics. Many more people--an estimated one-third of Earth's population--are infected with Mycobacterium tuberculosis, but most suppress the infection.

Typically, when M. tuberculosis invades the body, immune cells called macrophages engulf it. However, the microbe neutralizes the acids produced by the cells to destroy it. Trapped within the macrophages, TB persists in lungs and other organs without causing symptoms, says immunologist Stefan H.E. Kaufmann of the Max Planck Institute for Infection Biology in Berlin.

But if a person's immune defenses become weakened, the bacteria can escape their macrophage jails and spread to other cells--causing the cough, fever, and malaise that mark active TB, Kaufmann says.

Macrophages similarly engulf BCG. But being weaker than the TB microbe, it doesn't escape and cause infection. But unfortunately, it triggers only a lackluster immune response.

Kaufmann and his colleagues genetically altered BCG so that it makes a protein that punctures the sac in which a macrophage sequesters it. That causes the cell to commit suicide, unleashing the microbe's full complement of proteins for immune-cell inspection and provoking an intense immune response, Kaufmann says.

He and his team vaccinated mice with the new vaccine, which they call delta-ureC hly+ rBCG. After exposing the mice to TB, the researchers found less buildup of TB microbes in the animals' lungs than they observed in mice getting BCG. The new formulation, but not BCG, defended against an antibiotic-resistant form of TB called the Beijing/W strain, Kaufmann says.

The impressive immune responses that Kaufmann's team recorded indicate that this new vaccine can instigate the manufacture of immune system cells that specifically target M. tuberculosis, says Gunter Harth, an immunologist at the University of California, Los Angeles. "This certainly looks very convincing," he concludes.

Several research groups are testing other new TB vaccines (SN: 12/11/04, p. 382). "I think we need a combination of vaccines to kill a beast like TB," says Kaufmann.