Abstract
A fusion protein designated CSU-F36 was constructed that consisted of acylated Rv1411, a potent Toll-like receptor-2 agonist, fused to ESAT-6, a well-characterized immunogenic protein from Mycobacterium tuberculosis. The CSU-F36 fusion protein strongly induced interleukin 12 secretion from macrophages and induced the increased accumulation of CD4 T cells capable of secreting gamma interferon in the lungs of infected mice. These mice were significantly protected from low-dose aerosol challenge with M. tuberculosis, even with CSU-F36 delivered in a simple depot material. This "natural adjuvant"-containing system could potentially bypass the need for more expensive TH1-inducing adjuvants and could be applied to many mycobacterial proteins to provide effective and cheap new vaccines against tuberculosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / metabolism
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Adjuvants, Immunologic / pharmacology
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Animals
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Antigens, Bacterial / genetics
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Antigens, Bacterial / immunology
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Antigens, Bacterial / metabolism
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BCG Vaccine / immunology
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BCG Vaccine / pharmacology
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Interleukin-12 / immunology
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Lung / immunology
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Lung / pathology
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Mice
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Mice, Inbred C57BL
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Mycobacterium tuberculosis / immunology*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism
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Toll-Like Receptor 2 / agonists
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Toll-Like Receptor 2 / immunology*
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Toll-Like Receptor 2 / metabolism
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Tuberculosis, Pulmonary / immunology*
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Tuberculosis, Pulmonary / pathology
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Tuberculosis, Pulmonary / prevention & control*
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology*
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Vaccines, Synthetic / pharmacology
Substances
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Adjuvants, Immunologic
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Antigens, Bacterial
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BCG Vaccine
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Recombinant Fusion Proteins
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Tlr2 protein, mouse
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Toll-Like Receptor 2
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Vaccines, Synthetic
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Interleukin-12