title: Comparison of BCG prime-DNA booster and rBCG regimens for protection against tuberculosis.
abstract: Developing an effective adult prophylaxis vaccine is a high priority in the global control of tuberculosis (TB), because TB remains an important public health problem and the current widely used BCG vaccine provides effective protection only for children but variable protection against adult TB. BCG priming-heterologous vaccines booster and recombinant BCG technologies have been thought as two important regimens for inducing effective protection against adult TB. Obviously, defining the protective efficacy of the two regimens would benefit more rational design of the future adult TB vaccines. In this study, a recombinant BCG strain (rBCG::685A) expressing the fusion protein of ESAT-6 and Ag85A (r685A) of Mycobacterium tuberculosis was constructed successfully and the secretion of r685A protein from rBCG strain was confirmed by western blotting with anti-ESAT-6 and anti-Ag85A polyclonal antibodies, respectively. The immune responses and protective effects in rBCG::685A vaccinated C57BL/6 mice were compared with that of our previous reported BCG prime-pcD685A booster regimen. Boosting BCG with pcD685A DNA elicited higher level of r685A protein specific IFN-γ secreted by splenocytes and a more significant increase of both TNF-α and iNOS responses in the lung, thus providing better control of bacterial growth in both lung and spleen of immunized mice challenged with virulent M. tuberculosis, compared with mice vaccinated with rBCG::685A or BCG alone. Our results have implications for development of more effective adult TB vaccines for improved control of TB.
authors.affiliation: Department of Pathogen Biology; Lab of Bio-safety, School of Preclinical Medicine; Tongji Medical College; Huazhong University of Science & Technology; Wuhan, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tan
authors.affiliation: Department of Pathogen Biology; Lab of Bio-safety, School of Preclinical Medicine; Tongji Medical College; Huazhong University of Science & Technology; Wuhan, PR China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Pathogen Biology; Lab of Bio-safety, School of Preclinical Medicine; Tongji Medical College; Huazhong University of Science & Technology; Wuhan, PR China.
authors.forename: Xindong
authors.initials: X
authors.lastname: Teng
authors.affiliation: Department of Pathogen Biology; Lab of Bio-safety, School of Preclinical Medicine; Tongji Medical College; Huazhong University of Science & Technology; Wuhan, PR China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology; Lab of Bio-safety, School of Preclinical Medicine; Tongji Medical College; Huazhong University of Science & Technology; Wuhan, PR China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathogen Biology; Lab of Bio-safety, School of Preclinical Medicine; Tongji Medical College; Huazhong University of Science & Technology; Wuhan, PR China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Pathogen Biology; Lab of Bio-safety, School of Preclinical Medicine; Tongji Medical College; Huazhong University of Science & Technology; Wuhan, PR China.
authors.forename: Xionglin
authors.initials: X
authors.lastname: Fan
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D016207:Cytokines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D052247:Nitric Oxide Synthase Type II; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis
keywords: DNA vaccine; ESAT-6-Ag85A; prime-boost; recombinant BCG; tuberculosis