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CDC HIV/AIDS/Viral Hepatitis/STD/TB Prevention News Update
UNITED STATES: TB Vaccine Shows Promise in Mice: Study

November 21, 2011
Agence France Presse (09.04.11) - Monday, November 21, 2011

Researchers led by William Jacobs of Albert Einstein College of Medicine in New York believe they have made a "significant step" in the development of a safe and reliable vaccine against tuberculosis.

To better understand how Mycobacterium tuberculosis circumvents the human immune system, the team's strategy was to work with a closely related bacterium, Mycobacterium smegmatis, which is lethal to mice at high doses but not harmful to humans. They created a version of M. smegmatis lacking the ESX-3 genes that allow the bacterium to evade host immunity.

As anticipated, the mice did not become sick, even when injected with large doses of altered M. smegmatis. Without ESX-3, the modified bacterium could not penetrate the mice's immune systems, which fought off infection using the same T- cells that a successful TB vaccine would need to activate.

However, removing the same set of ESX-3 genes from M. tuberculosis killed the bacterium, meaning it could no longer be manipulated for the creation of a successful vaccine. The researchers then took another approach: They created a hybrid of the two bacteria by inserting the immune system-fighting ESX-3 genes from M. tuberculosis in the version of M. smegmatis from which the gene set had been removed.

The hybrid allowed the mice to once again fight off infection. Eight weeks later, they were exposed to high doses of M. tuberculosis, which is as lethal in mice as in humans. The "vaccinated" mice lived for an average 135 days compared to 54 days for the control group. Further, "vaccinated animals that survived more than 200 days had livers that were completely clear of TB bacteria, and nobody has ever seen that before," said Jacobs.

Only one-fifth of the mice showed such resilience, meaning that the vaccine needs improving, the team cautioned. "We don't even know yet if it will work in humans," Jacobs said. "But it is certainly a significant step." The study, "A Recombinant Mycobacterium Smegmatis Induces Potent Bactericidal Immunity Against Mycobacterium Tuberculosis," was published online in the journal Nature Medicine (2011;doi:10.1038/nm.2420).