結核ワクチン作製の試み

Abstract

A novel recombinant BCG (BCG-DHTM), that was deficient in urease, expressed with gene encoding the fusion of BCG-derived HSP70 and M. tuberculosis-derived major membrane protein (MMP)-II, was constructed for use as a vaccine against tuberculosis. BCG-DHTM efficiently activated dendritic cells (DC) to induce cytokine production, including IL-12, TNFalpha and IL-1beta and phenotypic changes. The DC infected BCG-DHTM was more potent in activation of native T cells of CD4 and CD8 subsets than those infected vector control BCG. The activation of naïve T cells by BCG-DHTM was closely associated with phagomal maturation, and that of naïve CD8+ T cells by BCG-DHTM was induced by the activation of cytosolic cross-presentation pathway. Further, BCG-DHTM seemed to activate native CD4+ T cells and native CD8+ T cells by antigen-specific fashion. The primary infection of BCG-DHTM in C57BL/6 mice for 12 weeks efficiently produced T cells responsive to in vitro secondary stimulation with MMP-II, HSP70 and H37Rv-derived cytosolic protein and inhibited with multiplication of subsequently challenged M. tuberculosis in lungs at least partially. The effect of BCG-DHTM as a vaccine for tuberculosis is not fully convincing and need the improvement, however, our strategy in the development of new recombinant BCG for tuberculosis seems to provide useful tool.