Abstract
Background:
The tuberculosis (TB) pandemic remains a leading cause of human morbidity and mortality, despite widespread use of the only licensed anti-TB vaccine, bacille Calmette-Guerin (BCG). The protective efficacy of BCG in preventing pulmonary TB is highly variable; therefore, an effective new vaccine is urgently required.
Methods:
In the present study, we assessed the ability of novel recombinant BCG vaccine (rBCG) against Mycobacterium tuberculosis by using modern immunological methods.
Results:
Enzyme-linked immunospot assays demonstrated that the rBCG vaccine, which coexpresses two mycobacterial antigens (Ag85B and CFP10) and human interleukin (IL)-12 (rBCG2) elicits greater interferon-γ (IFN-γ) release in the mouse lung and spleen, compared to the parental BCG. In addition, rBCG2 triggers a Th1-polarized response. Our results also showed that rBCG2 vaccination significantly limits M. tuberculosis H37Rv multiplication in macrophages. The rBCG2 vaccine surprisingly induces significantly higher tumor necrosis factor-α (TNF-α) production by peripheral blood mononuclear cells that were exposed to a nonmycobacterial stimulus, compared to the parental BCG.
Conclusion:
In this study, we demonstrated that the novel rBCG2 vaccine may be a promising candidate vaccine against M. tuberculosis infection.
Keywords:
Mycobacterium tuberculosis; recombinant bacille Calmette–Guerin; vaccine.
Copyright © 2014. Published by Elsevier B.V.
MeSH terms
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Acyltransferases / administration & dosage
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Acyltransferases / genetics
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Acyltransferases / immunology*
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Adjuvants, Immunologic / administration & dosage*
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Adjuvants, Immunologic / genetics
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Animals
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Antigens, Bacterial / administration & dosage
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Antigens, Bacterial / genetics
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Antigens, Bacterial / immunology*
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Bacterial Proteins / administration & dosage
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Bacterial Proteins / genetics
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Bacterial Proteins / immunology*
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Enzyme-Linked Immunospot Assay
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Female
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Humans
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Interferon-gamma / metabolism
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Interleukin-12 / administration & dosage*
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Interleukin-12 / genetics
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Leukocytes, Mononuclear / immunology
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Lung / immunology
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Macrophages / immunology
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Macrophages / microbiology
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mycobacterium bovis / genetics
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Mycobacterium bovis / immunology*
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Mycobacterium tuberculosis / growth & development
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Mycobacterium tuberculosis / immunology
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Spleen / immunology
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Th1 Cells / immunology
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Tuberculosis / prevention & control*
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Tuberculosis Vaccines / administration & dosage
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Tuberculosis Vaccines / genetics
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Tuberculosis Vaccines / immunology*
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Tumor Necrosis Factor-alpha / metabolism
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
Substances
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Adjuvants, Immunologic
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Antigens, Bacterial
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Bacterial Proteins
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CFP-10 protein, Mycobacterium tuberculosis
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Tuberculosis Vaccines
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Tumor Necrosis Factor-alpha
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Vaccines, Synthetic
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Interleukin-12
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Interferon-gamma
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Acyltransferases
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antigen 85B, Mycobacterium tuberculosis