A novel recombinant BCG-expressing pro-apoptotic protein BAX enhances Th1 protective immune responses in mice.
One-third of the world's population is infected with Mycobacterium tuberculosis (MTB). The protective efficacy of bacille Calmette Guérin (BCG) vaccine against tuberculosis (TB) in adults is highly controversial even though the BCG vaccine has been available for more than 90 years. Because BCG is effective against infantile tuberculosis meningitis and miliary tuberculosis in young children and provides cost-effective prevention from tuberculosis for developing countries, it would be desirable to modify the existing BCG vaccine to provide more comprehensive protection. In our study, we constructed a novel recombinant BCG strain expressing pro-apoptotic BAX (rBCG::BAX) and demonstrated that it significantly induced the apoptosis of macrophages infected with rBCG::BAX both in vitro and in vivo. In addition, it significantly enhanced Ag85B-specific IFN-γ enzyme-linked immunospot responses, IFN-γ secretion, IL-2 secretion and the ratio of Ag85B-specific IgG2b/IgG1, and it significantly decreased Ag85B-specific IL-4. Furthermore, it presumably facilitated antigen presentation by inducing a significant up-regulation in the expression of MHC-II and B7.1 (CD80) co-stimulatory molecules on macrophages. In conclusion, these results suggest that the rBCG::BAX strain elicited predominantly a Th1 protective immune responses and might be a potential tuberculosis vaccine candidate for further study.
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, People's Republic of China; Medical College, Hexi University, Zhangye, Gansu 734000, People's Republic of China.
Guanghua
G
Li
Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, People's Republic of China.
Guoyuan
G
Liu
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, People's Republic of China.
Na
N
Song
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, People's Republic of China.
Cong
C
Kong
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, People's Republic of China.
Qi
Q
Huang
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, People's Republic of China.
Haibo
H
Su
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, People's Republic of China; Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People's Republic of China.
Aixiao
A
Bi
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, People's Republic of China; Shanghai Pulmonary Hospital, Medical School, Tongji University, Shanghai 200433, People's Republic of China.
Liulin
L
Luo
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, People's Republic of China.
Lin
L
Zhu
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, People's Republic of China. Electronic address: yingxu2520@fudan.edu.cn.
Ying
Y
Xu
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai 200438, People's Republic of China. Electronic address: hhwang@fudan.edu.cn.
Honghai
H
Wang
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D017951:Antigen Presentation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000737:chemistry / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C494827:Bax protein, mouse; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D051028:bcl-2-Associated X Protein; D015847:Interleukin-4; D007371:Interferon-gamma
Apoptosis; BAX; Recombinant BCG; Tuberculosis; Vaccine