A novel recombinant BCG-expressing pro-apoptotic protein BAX enhances Th1 protective immune responses in mice |
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| Affiliation: | 1. 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;2. Medical College, Hexi University, Zhangye, Gansu 734000, People''s Republic of China;3. Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, People''s Republic of China;4. Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People''s Republic of China;5. Shanghai Pulmonary Hospital, Medical School, Tongji University, Shanghai 200433, People''s Republic of China;1. USC Norris Comprehensive Cancer Center, Molecular and Computational Biology Program, Department of Biological Sciences; Departments of Pathology, Biochemistry and Molecular Biology, Molecular Microbiology and Immunology, Urology, University of Southern California Keck School of Medicine, 1441 Eastlake Ave., Rm. 5428, Los Angeles, CA 90089-9176, United States;2. Department of Microbiology and Molecular Genetics, Michigan State University, 5175 Biomedical Physical Sciences, East Lansing, MI 48824, United States;1. The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China;2. Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China;3. Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China;1. Department of Medical Immunology, Medical School, Anhui University of Science and Technology, China;2. Medical Inspection Center, Anhui University of Science and Technology, Huainan, China;3. Affiliated Cancer Hospital, Anhui University of Science and Technology, China;1. Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo 315211, China;2. Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture, Ningbo University, Ningbo 315211, China;1. Department of Paediatrics, University of Oxford, Oxford, UK;2. NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK;3. Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK;1. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA;2. Department of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA;3. Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA |
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| Abstract: | 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. |
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| Keywords: | Tuberculosis Vaccine Recombinant BCG Apoptosis BAX |
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