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Clin Vaccine Immunol. 2009 Aug;16(8):1121-6. doi: 10.1128/CVI.00112-09. Epub 2009 Jun 10.

Recombinant Mycobacterium bovis BCG expressing the chimeric protein of antigen 85B and ESAT-6 enhances the Th1 cell-mediated response.

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1
State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, PR China.

Abstract

The chimeric protein that relies on the T-cell epitopes of antigen 85B (Ag85B) and the 6-kDa early secreted antigen target (ESAT-6) has been demonstrated to augment the Th1 immune response. In this study, we developed a recombinant Mycobacterium bovis BCG (rBCG) strain that secretes the chimeric protein of Ag85B and ESAT-6 (rBCG-A(N)-E-A(C)). Immunization with this rBCG strain induced stronger antigen-specific gamma interferon (IFN-gamma) activities, as determined by an enzyme-linked immunospot assay, and higher levels of antigen-specific CD4(+) and CD8(+) T-cell responses than those in the control groups immunized with either rBCG expressing the Ag85B-ESAT-6 fusion protein (rBCG-A-E) or BCG. Likewise, rBCG-A(N)-E-A(C) significantly increased the level of production of the major Th1 cytokines IFN-gamma and tumor necrosis factor alpha in splenocyte cultures to levels comparable to those elicited by control BCG. Moreover, the antigen-specific immunoglobulin 2c (IgG2c)/IgG1 ratio for mice immunized with rBCG-A(N)-E-A(C) was also much higher than the ratios for the other immunized groups. Together, these results indicate that this rBCG-A(N)-E-A(C) strain enhances the Th1 cell-mediated response and may serve as a potential vaccine against M. tuberculosis.

PMID:
19515867
PMCID:
PMC2725546
DOI:
10.1128/CVI.00112-09
[Indexed for MEDLINE]
Free PMC Article
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