Pockets of Resistance

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Science  25 Feb 2005:
Vol. 307, Issue 5713, pp. 1173
DOI: 10.1126/science.307.5713.1173b

Although only 5% of those exposed to mycobacteria go on to develop acute tuberculosis, many suffer latent infections that have escaped antibiotic treatment and may recrudesce with stress or aging. Ha et al. tested a combined vaccine-chemotherapy regime for its ability to prevent reactivation of disease in mice infected with Mycobacterium tuberculosis. Although protective antigens have not yet been defined precisely for tuberculosis, these authors made a DNA vaccine in a pGX10 vector containing two genes they had tested previously: Ag85A epitopes (recognized by CD4+ T cells) are expressed on the surface of macrophages during early infection and PstS-3 epitopes (recognized by both CD4+ and CD8+ T cells) during late phase. Four weeks after infection, they administered the vaccine to mice along with the drugs isoniazid and pyrazinamide. Subsequent treatment with dexamethasone reactivated the disease in the control groups of mice but not in the vaccinated and antibiotic-dosed mice, suggesting that combining the boosting of the immune response with drugs had eliminated the mycobacteria. — CA

Gene Ther. 10.1038/ (2005).

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