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Recombinant BCG coexpressing Ag85B,ESAT-6 and Rv3620c elicits specific Th1 immune responses in C57BL/6 mice
Institution:1. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China;2. Rizhao Polytechnic, Rizhao, Shandong 200433, China;1. Dept. of Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Soura, Srinagar, Kashmir, J&K 190011, India;2. Dept. of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Soura, Kashmir, J&K 190011, India;3. Dept. of General Surgery, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Soura, Kashmir, J&K 190011, India;1. Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1374, São Paulo, SP 05508-900, Brazil;2. Department of Endodontics, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, São Paulo, SP 05508-900, Brazil;3. Department of Electron Microscopy, Adolfo Lutz Institute, Av Dr. Arnaldo, 355, São Paulo, SP 01246-902, Brazil;1. Nucleo de Medicina Tropical, Universidade Federal do Para, Belem, PA, Brazil;2. Centro de Ciencias Biologicas e da Saude, Universidade do Estado do Para, Belem, PA, Brazil;3. Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil;1. Department of Periodontology, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan;2. Department of Dentistry and Oral Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan;3. Oral Health Science Center, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan;1. Departamento de Óptica, Farmacología y Anatomía, Universidad de Alicante, Alicante, Spain;2. Departamento de Microbiología y Ecología, Universitat de València, Burjassot, Spain
Abstract:Tuberculosis (TB) remains to be an enormous global health problem. The inconsistent protection efficacy of Bacille Calmette-Guérin (BCG) calls for new vaccines for TB. One choice to improve the efficacy of BCG vaccine is recombinant BCG (rBCG). Experimental evidences have revealed that Ag85B, ESAT-6 and Rv3620c are important immunodominant antigens of Mycobacterium tuberculosis. In this study, we have constructed a novel rBCG expressing fusion protein Ag85B-ESAT6-Rv3620c and evaluated the immunogenicity of this rBCG in C57BL/6 mice. Results show that there is a strong TB-specific CD4+ and CD8+ T lymphocytes proliferation in mice immunized with this rBCG vaccine. A single dose immunization of rBCG could induce a significantly strong Th1 immune response characterized by an increasing ratio of antigen-specific IgG2b/IgG1 as well as a high expression level of Th1 cytokines such as IFN-γ, TNF-α and IL-2. This conclusion was confirmed by a decreased secretion of Th2 cytokine IL-10. Moreover, this rBCG induced a strong humoral response in mice with an increasing antigen-specific IgG titer. Therefore, we concluded that this rBCG could significantly increase both Th1 type cellular immune response and antigen-specific humoral response compared with BCG. The above observations demonstrated that rBCG::Ag85B-ESAT6-Rv3620c is a potential candidate vaccine against M. tuberculosis for further study.
Keywords:rBCG  Th1  Cytokines  Vaccine
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