Engineered Autophagy Boosts BCG Protective Immunity May Result in New Strategies for TB Vaccine Development
Scientists have found that when components of M. tuberculosis (Mtb), the bacterium that cause tuberculosis (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the TB vaccine Bacille Calmette-Guérin (BCG) and processed through autophagy—a mechanism that body cells use to recycle outdated and damaged components and turn them into new building blocks—they create stronger and longer lasting immunity.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 the development of new, powerful TB vaccines.
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| Dr. Chinnaswamy Jagannath, Ph.D. |
BCG is one of the most widely used vaccines in the world. It protects children from primary TB but fails to protect adults from active disease. The variable efficacy of BCG vaccination against TB prompted lead investigator, Dr. Chinnaswamy Jagannath, Ph.D., University of Texas Health Science Center at Houston, and his team to study the ways that BCG evades immune-stimulating mechanisms and to devise ways to neutralize them.
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.
C Jagannath 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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