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
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
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,"
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