Evidence for absence of the MPB64 gene in some substrains of Mycobacterium bovis BCG

Li, Huayi; Ulstrup, Jan C.; Jonassen, Tom Øystein; Melby, K; Nagai, Shoichiro; Harboe, Morten

doi:10.1128/iai.61.5.1730-1734.1993

Cited by 94 publications

(46 citation statements)

References 23 publications

(18 reference statements)

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“…The gene, however, has been deleted from some strains of the vaccine form of Myco. bovis (BCG) during multiple subcultures from the original isolate [20]. The absence of mpb64 from the commonly used strains BCG-Pasteur and BCG-Glaxo and their derivatives, including BCG-CSL, results in significant differences in the proliferative responses to the protein between BCG vaccinees and subjects infected with Myco.…”

Section: Discussionmentioning

confidence: 99%

Expression of Mycobacterium tuberculosis MPT64 in recombinant Myco. smegmatis: purification, immunogenicity and application to skin tests for tuberculosis

Roche

Winter

Triccas

et al. 1996

Clinical and Experimental Immunology

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SUMMARYProteins secreted across the cell wall of mycobacteria are important antigens recognized early in the host response to mycobacterial infection. MPT64 is a 23-kD secreted protein restricted to members of the Mycobacterium tuberculosis complex which elicits T cell responses and cutaneous DTH reactions in Myco. tuberculosis-infected animals. Patients with tuberculosis and their tuberculin-positive contacts respond to the protein, but recipients of bacille Calmette-Guérin (BCG) vaccine strains lacking the mpt64 gene do not. In the present study, we describe the development of a unique recombinant mycobacterial vector which secretes the encoded Myco. tuberculosis protein MPT64 at high levels into the culture filtrate, from which the protein is isolated by a single-step affinity chromatographic step. The purified protein was recognized by both polyclonal and monoclonal anti-MPT64 antibodies. The T cell reactivity of the protein was confirmed by its ability to stimulate human anti-rMPB64 T cell lines. The Myco. smegmatis recombinant MPT64 protein was superior to the Escherichia coli rMPB64 protein, which has identical amino acid sequence, in eliciting cutaneous DTH reactions in guinea pigs sensitized with Myco. tuberculosis. Animals sensitized with BCG strains lacking the mpb64 gene failed to respond to MPT64. Similarly, interferon-gamma (IFN-) responses in tuberculosis patients and their contacts were higher to the Myco. smegmatis form of the protein. The potential of this form of the Myco. tuberculosis MPT64 protein as a skin test reagent for tuberculosis is discussed.

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Section: Discussionmentioning

confidence: 99%

Expression of Mycobacterium tuberculosis MPT64 in recombinant Myco. smegmatis: purification, immunogenicity and application to skin tests for tuberculosis

Roche

Winter

Triccas

et al. 1996

Clinical and Experimental Immunology

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“…MPT64 is so far the only secreted antigen with no intermediate position in the cell wall [143]. MPT64 is only found in some substrains of BCG such as the Tokyo, Morau, Russia and Sweden strains, whereas BCG Danish 1331, Pasteur, Glaxo and Tice strains lack the gene encoding this molecule [169]. The gene encoding MPT64 is part of a 10.7 kb DNA segment (RD2) deleted in these strains and this mutation may have occurred at a relatively late timepoint during the development of the BCG substrains [170].…”

Section: Culture Filtrate Proteinsmentioning

confidence: 99%

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

1997

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Andersen P. Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis. Scand J Immunol 1997;45:115-131 Tuberculosis (TB) is the largest single infectious cause of human mortality. The incidence of TB has remained high in most of the developing world and the disease has recently re-emerged as a public health problem in industrialized countries. The development of a new improved TB vaccine is a highly prioritized international research area, which has been further stimulated by the appearance of multi-drug resistant strains of Mycobacterium tuberculosis. The present status of the attempts to characterize the protective immune response to TB will be reviewed with special emphasis on recent progress in the identification and characterization of target molecules recognized by protective cells. This paper will focus on proteins released from live bacteria and discuss their role in the host-pathogen interaction and the ongoing attempts to use these molecules in TB subunit vaccines.

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“…To maximize exposure to mycobacterial proteins during the development of vaccine responses, it is important that the BCG strain is metabolically active to produce sufficient amount of target antigens before the BCG 'infection' is cleared. On the other hand, the elevated expression of certain antigens, such as MPB70 ⁄ 83 [10,11] and proteins of the RD2region (6,9,30), leads to increased exposure of mycobacterial immunogens to the host and can eventually result in improved immune responses and accelerated elimination of the bacilli.…”

Section: Discussionmentioning

confidence: 99%

“…After it was proved to confer protection against tuberculosis in humans, it was distributed to laboratories around the world for local maintenance and administration. The continued passages at separate facilities led to a divergence in genetic and proteomic content, as shown in several proteomic [4][5][6] and genomic studies [7,8]. Strains phylogenetically closest to the virulent M. bovis strain are often referred to as 'early' strains, while those that differ more are called 'late' strains.…”

Section: Introductionmentioning

confidence: 99%

“…Strains phylogenetically closest to the virulent M. bovis strain are often referred to as 'early' strains, while those that differ more are called 'late' strains. The most impor-tant differences between these strains are traditionally seen to include the loss of the region of difference 2 (RD2) [6,9] and a reduced expression of MPB70 and MPB83 [10,11] in the 'late' strains. However, in vitro cultivation also lead to other modifications such as duplications and upregulation of gene expression, which affected the various BCG strains differently [8,12].…”

Section: Introductionmentioning

confidence: 99%

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Long‐Term Persistence of BCG Pasteur in Lungs of C57BL/6 Mice Following Intranasal Infection

et al. 2012

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Different Mycobacterium bovis Bacillus Calmette‐Guérin (BCG) vaccine substrains may vary in their efficacy. Here, we describe differences in disease progression and pathology in the lungs of female C57BL/6 mice infected intranasally with BCG Russia or BCG Pasteur and followed for 17 months. The lungs were investigated for bacillary load, histopathology and expression of cytosolic and secreted proteins by immunohistochemistry. BCG Russia was cleared from the lungs by 8 months. BCG Pasteur reached a low‐level persistence at 8 months and remained at this level until the end of the experiment. BCG Pasteur induced greater pathology than BCG Russia, and there were more macrophage and lymphocyte infiltrates in animals infected with BCG Pasteur (P < 0.05). Bacterial growth correlated with cellular infiltration. All selected mycobacterial proteins were found to be expressed in the lesions by both BCG strains, and there were only minor variations between the strains. Furthermore, we identified isolated cells containing a high mycobacterial protein load in the normal‐looking lung parenchyma. The infected cells in the healthy areas of the lung may represent the ability of mycobacteria to evade immune activation and thereby persist in the host. Clearance of BCG Russia indicates that a more effective and sterilizing immune response is established by this strain. On the other hand, the ability of BCG Pasteur to persist could be important for long‐term protection against challenge with Mycobacterium tuberculosis.

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Evidence for absence of the MPB64 gene in some substrains of Mycobacterium bovis BCG

Cited by 94 publications

References 23 publications

Expression of Mycobacterium tuberculosis MPT64 in recombinant Myco. smegmatis: purification, immunogenicity and application to skin tests for tuberculosis

Expression of Mycobacterium tuberculosis MPT64 in recombinant Myco. smegmatis: purification, immunogenicity and application to skin tests for tuberculosis

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

Long‐Term Persistence of BCG Pasteur in Lungs of C57BL/6 Mice Following Intranasal Infection

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