Abstract
Previously we have shown that Ag85B-ESAT-6 is a highly efficient vaccine against tuberculosis. However, because the ESAT-6 Ag is also an extremely valuable diagnostic reagent, finding a vaccine as effective as Ag85B-ESAT-6 that does not contain ESAT-6 is a high priority. Recently, we identified a novel protein expressed by Mycobacterium tuberculosis designated TB10.4. In most infected humans, TB10.4 is strongly recognized, raising interest in TB10.4 as a potential vaccine candidate and substitute for ESAT-6. We have now examined the vaccine potential of this protein and found that vaccination with TB10.4 induced a significant protection against tuberculosis. Fusing Ag85B to TB10.4 produced an even more effective vaccine, which induced protection against tuberculosis comparable to bacillus Calmette-Guerin vaccination and superior to the individual Ag components. Thus, Ag85B-TB10 represents a new promising vaccine candidate against tuberculosis. Furthermore, having now exchanged ESAT-6 for TB10.4, we show that ESAT-6, apart from being an excellent diagnostic reagent, can also be used as a reagent for monitoring vaccine efficacy. This may open a new way for monitoring vaccine efficacy in clinical trials.
Publication types
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Research Support, Non-U.S. Gov't
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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Amino Acid Sequence
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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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Base Sequence
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / microbiology
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Colony Count, Microbial
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism
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Female
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Interferon-gamma / biosynthesis
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Lung / immunology
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Lung / microbiology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Molecular Sequence Data
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology*
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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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Tuberculosis, Pulmonary / diagnosis
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Tuberculosis, Pulmonary / immunology
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Tuberculosis, Pulmonary / prevention & control
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology*
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Vaccines, Subunit / administration & dosage
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Vaccines, Subunit / genetics
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Vaccines, Subunit / immunology
Substances
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Antigens, Bacterial
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Bacterial Proteins
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ESAT-6 protein, Mycobacterium tuberculosis
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Epitopes, T-Lymphocyte
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Recombinant Fusion Proteins
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TB10.4 antigen, Mycobacterium tuberculosis
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Tuberculosis Vaccines
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Vaccines, DNA
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Vaccines, Subunit
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Interferon-gamma
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Acyltransferases
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antigen 85B, Mycobacterium tuberculosis