Recombinant Mycobacterium bovis BCG expressing the chimeric protein of antigen 85B and ESAT-6 enhances the Th1 cell-mediated response.
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.
Xu
Ying
Y
State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, PR China.
Liu
Wei
W
Shen
Hongbo
H
Yan
Jingran
J
Qu
Di
D
Wang
Honghai
H
D000217:Acyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007074:Immunoglobulin G; D032581:Tuberculosis Vaccines; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis