Strategy Improves Effectiveness of TB Vaccine

Combination approach boosts immune response in mice

A combination treatment using a cancer drug and genetically modified organisms was associated with a tenfold increase in killing tuberculosis cells in a mouse model, researchers in Texas report.

We still need animal models to validate better working vaccines prior to human studies.

—Chinnaswamy Jagannath, PhD, University of Texas Medical School at Houston

Their work suggests that the immune-boosting treatment can improve the efficacy of the bacille Calmette-Guérin (BCG) vaccine in humans, the researchers said.

BCG is the only tuberculosis vaccine approved for use in humans, but it is ineffective in adults and has variable efficacy in children. Therefore, improving its efficacy is "an urgent public health priority," said Chinnaswamy Jagannath, PhD, an associate professor at the University of Texas Medical School at Houston and first author of a paper describing the new immune-boosting strategy. (Jagannath C, Lindsey DR, Dhandayuthapani S, et al. Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nat Med. 2009;15(3):267-276.)

It is "too early to speculate" how the immune-boosting strategy would be formulated in combination with the BCG vaccine for clinical use, Dr. Jagannath said in an e-mail to PFQ. "We still need animal models to validate better working vaccines prior to human studies."

Tuberculosis hides in cells so that its antigens are not recognized by the immune system, and Dr. Jagannath and colleagues had previously shown that the BCG vaccine does the same thing, limiting its efficacy in triggering immune response. In the current study, the researchers showed that the cancer drug rapamycin enhanced the presentation of BCG antigens to the immune system.