Volunteer for NIAID-funded clinical studies related to tuberculosis on ClinicalTrials.gov.
Scientists have found that when components of Mycobacterium tuberculosis (Mtb), the bacterium that causes TB, are integrated into the TB vaccine Bacille Calmette-Guérin (BCG) and processed through autophagy—a mechanism that body cells use to recycle outdated and damaged components and turn them into new building blocks—they create stronger and longer lasting immunity. The NIAID-supported work, published in Nature Medicine, may enhance BCG protection, as well as provide a simple and powerful strategy for developing new, powerful TB vaccines.
Both BCG and Mtb present immunogenic proteins or antigens to the immune system when they invade host cells, but this does not result in long lasting-immunity. The scientists hypothesized that a drug used for organ transplantation, Rapamycin, which modulates the movement of proteins within cells, would cause BCG immunogenic proteins and antigens to enter pathways leading to improved immunization.
Working in a mouse model, the scientists found that genetically processed Mtb immunogenic proteins or antigens that were processed and presented to the immune system by Rapamycin-induced autophagy stimulated a superior immune response. This dual approach to the BCG vaccine was associated with a tenfold increase in the number of TB organisms killed and a threefold increase in the duration of protection in tests with mice, according to Dr. Jagannath.
These findings potentially present a new method to enhance vaccine efficacy by engineering access to the autophagy pathway. Encouraged by study results, the team plans to build upon their work before entering clinical trials.
Jagannath C et al. Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nature Medicine DOE: 10.1038 (2009)
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Last Updated June 16, 2009