Cloning and Sequencing of a Unique Antigen MPT70 from Mycobacterium tuberculosis H37Rv and Expression in BCG Using E. coli‐Mycobacteria Shuttle Vector

Matsumoto, Sohkichi; Matsuo, Takemitsu; Ohara, Naoya; Hotokezaka, Hitoshi; Naito, Mariko; Minami, Junzaburo; Yamada, Takeshi

doi:10.1111/j.1365-3083.1995.tb03565.x

Cited by 38 publications

(35 citation statements)

References 43 publications

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“…Although the magnitude of the observed therapeutic effect of plasmid expressing Hsp65 was somewhat less, the experiment had to be curtailed because the control mice that were untreated or received empty plasmid began to show clinical signs of advanced tuberculosis. In this experiment, either a plasmid expressing a 22K mycobacterial secretory antigen (MPT70) that may be upregulated in infection 18,19 , or a plasmid expressing interleukin-12 (IL-12; see below), was at least as bene®cial as a plasmid expressing Hsp65.…”

mentioning

confidence: 99%

Therapy of tuberculosis in mice by DNA vaccination

Lowrie

Tascon

Bonato³

et al. 1999

Nature

431

313

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Mycobacterium tuberculosis continues to kill about 3 million people every year, more than any other single infectious agent. This is attributed primarily to an inadequate immune response towards infecting bacteria, which suffer growth inhibition rather than death and subsequently multiply catastrophically. Although the bacillus Calmette-Guerin (BCG) vaccine is widely used, it has major limitations as a preventative measure. In addition, effective treatment requires that patients take large doses of antibacterial drug combinations for at least 6 months after diagnosis, which is difficult to achieve in many parts of the world and is further restricted by the emergence of multidrug-resistant strains of M. tuberculosis. In these circumstances, immunotherapy to boost the efficiency of the immune system in infected patients could be a valuable adjunct to antibacterial chemotherapy. Here we show in mice that DNA vaccines, initially designed to prevent infection, can also have a pronounced therapeutic action. In heavily infected mice, DNA vaccinations can switch the immune response from one that is relatively inefficient and gives bacterial stasis to one that kills bacteria. Application of such immunotherapy in conjunction with conventional chemotherapeutic antibacterial drugs might result in faster or more certain cure of the disease in humans.

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mentioning

confidence: 99%

Therapy of tuberculosis in mice by DNA vaccination

Lowrie

Tascon

Bonato³

et al. 1999

Nature

431

313

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“…The internalization of live BCG into the HeLa cells was found in their cytoplasm with cytochalasin B [3] (100 μg/ml, Figure 3E) or heparin [4] (0.001 U/ml.Figure 3F) was added into each well before co-culture with HeLa cell respectively. Immunoelectron microscope checked using polyclonal antibodies of the MPB70 (secreted protein, α-antigen) [5-7] and revealed the protein A gold reacted around the cell wall of live BCG. (Figure 3B, D)…”

Section: Resultsmentioning

confidence: 99%

“…MPB70 [7] (α antigen) known to be an immunogenic mycobacterial protein secreted in large amounts from culture filtrated of Mycobacterium bovis Bacillus Calmette-Guérin(BCG) Tokyo. This protein is thought to be crucial for binding phagocytic cell having fibronectin receptors and this function might be a direct effect of BCG immunotherapy[10,11].…”

Section: Discussionmentioning

confidence: 99%

Growth inhibition of HeLa cell by internalization of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) Tokyo

Kitamura

Mastumoto

Asahina

2009

Cancer Cell International

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BackgroundIntravesical BCG immunotherapy is effective for preventing recurrence and progression in none muscle-invasive bladder cancer but the dosing schedule and duration of treatment remain empirical. The mechanisms by which intravesical BCG treatment mediates antitumor activity are currently poorly understood.ResultsHeLa cell infected with Mycobacterium bovis Bacillus Calmette-Guérin(BCG) Tokyo which were different multiplicity of infection(MOI). Proliferation of HeLa cell reduced in a dose-dependent manner by live BCG. The cytoplasm of the HeLa cell showed variety lysosomal stages by internalized and interacted BCG.ConclusionProliferated Live BCG secreted the protein and depressed the growth of tumor. The possibility for clinical introduction of BCG therapy for carcinoma reported with review of literature.

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“…MPB70 is a typical soluble secreted protein highly specific for the M. tuberculosis complex [15,16]. The deduced amino acid (AA) sequence of the MPB70 protein of Mycobacterium bovis is identical to that of MPT70 of M. tuberculosis [17]. In mouse experiments, therapeutic effects have been achieved by use of MPT70 DNA immunization [6], and MPB70 has been suggested as a strong candidate in a subunit vaccine against human tuberculosis [18].…”

Section: Introductionmentioning

confidence: 99%

T‐ and B‐Cell Epitopes in the Secreted Mycobacterium bovis Antigen MPB70 in Mice

et al. 2003

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MPB70 is a soluble secreted protein highly expressed in Mycobacterium bovis and strains of bacille Calmette±Gue Ârin (BCG); as such, it is a candidate for subunit and DNA vaccines against tuberculosis. MPB70 was screened for T-cell epitopes in four different inbred mouse strains. Major histocompatibility complex (MHC) H-2 b -expressing mice (C57BL/6) secreted interferon-g (IFN-g) after stimulation with peptides from the regions 1±20, 41±50, 81±110, 121±150 and 161±193 of the MPB70 sequence. H-2 db mouse (B6D2) splenocytes secreted IFN-g after stimulation with some of the same peptides, whereas H-2 d mice (BALB/c and DBA/2) did not secrete IFN-g upon stimulation with the peptides. Sera from H-2 db mice immunized with native MPB70 in incomplete Freund's adjuvant (IFA), mpb70 DNA or live BCG Moreau were found to contain antibodies against the native MPB70 antigen. H-2 db mice immunized with native MPB70 in IFA exhibited high titres of peptide-reactive immunoglobulin G1 (IgG1) antibodies, whereas DNA-immunized mice reacted with IgG2a antibodies against some of the same peptides. As some of the epitopes recognized by mouse T and B cells have previously been found to stimulate immune responses in humans, cattle and rabbits, we conclude that these epitopes may be good general epitopes for the stimulation of T-and B-cell responses and candidates for a DNA vaccine with a broad applicability.

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Cloning and Sequencing of a Unique Antigen MPT70 from Mycobacterium tuberculosis H37Rv and Expression in BCG Using E. coli‐Mycobacteria Shuttle Vector

Cited by 38 publications

References 43 publications

Therapy of tuberculosis in mice by DNA vaccination

Therapy of tuberculosis in mice by DNA vaccination

Growth inhibition of HeLa cell by internalization of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) Tokyo

T‐ and B‐Cell Epitopes in the Secreted Mycobacterium bovis Antigen MPB70 in Mice

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