title: A novel recombinant Mycobacterium bovis bacillus Calmette-Guerin strain expressing human granulocyte macrophage colony-stimulating factor and Mycobacterium tuberculosis early secretory antigenic target 6 complex augments Th1 immunity.
abstract: Since Mycobacterium bovis bacillus Calmette-Guerin strain (BCG) fails to protect adults from pulmonary tuberculosis (TB), there is an urgent need for developing a new vaccine. In this study, we constructed a novel recombinant BCG strain (rBCG) expressing human granulocyte macrophage colony-stimulating factor (GM-CSF) and the 6 kDa early secretory antigenic target (ESAT6) of Mycobacterium tuberculosis, named rBCG:GE (expressing GMCSF-ESAT6 complex), and evaluated the immunogenicity of the construct in BALB/c mice. Our results indicated that the rBCG:GE was able to induce higher titer of antibody than the conventional BCG, the rBCG:G (expressing GM-CSF) and the rBCG:E (expressing ESAT6). Moreover, the rBCG:GE also elicited a longer-lasting and stronger Th1 cellular immune responses than the other groups, which was confirmed by the incremental proliferation of splenocytes, the increased percentages of CD4(+) and CD8(+) T cells of spleen, the elevated level of interferon-γ in splenocyte culture after tuberculin-purified protein derivative stimulation, and the increased concentration of GM-CSF in serum. The data presented here suggested the possibility that the recombinant BCG:GE might be a good vaccine candidate to TB.
authors.affiliation: Laboratory of Infection and Immunity, School of Basic Medicine, West China Center of Medical Sciences, Sichuan University, Chengdu, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.forename: Lang
authors.initials: L
authors.lastname: Bao
authors.forename: Yihao
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000328:Adult; D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis*; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000096:biosynthesis
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011994:Recombinant Proteins; D032581:Tuberculosis Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor