scholarly journals MTSA-10, the Product of the Rv3874 Gene of Mycobacterium tuberculosis, Elicits Tuberculosis-Specific, Delayed-Type Hypersensitivity in Guinea Pigs

2000 ◽  
Vol 68 (2) ◽  
pp. 990-993 ◽  
Author(s):  
Roberto Colangeli ◽  
John S. Spencer ◽  
Pablo Bifani ◽  
Alan Williams ◽  
Konstantin Lyashchenko ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Skin Test ◽  
Mycobacterium Bovis ◽  
Mycobacterium Avium ◽  
Guinea Pigs ◽  
Nontuberculous Mycobacteria ◽  
Specific Antigen ◽  
Delayed Type Hypersensitivity ◽  
New Skin

ABSTRACT In a search for new skin test reagents specific for tuberculosis, we found that the antigen encoded by gene Rv3874 of Mycobacterium tuberculosis elicited delayed-type hypersensitivity in M. tuberculosis-infected guinea pigs but not in control animals immunized with Mycobacterium bovis bacillus Calmette-Guérin (BCG) or Mycobacterium avium. The antigen, which was named MTSA-10 (for M. tuberculosis-specific antigen 10), is a prime candidate for a component of a new tuberculin that will allow discrimination by a skin test of latent M. tuberculosis infection from vaccination with BCG or from sensitization with environmental, nontuberculous mycobacteria.

scholarly journals Delayed-Type Hypersensitivity Responses to ESAT-6 and MPT64 from Mycobacterium tuberculosis in the Guinea Pig

1998 ◽  
Vol 66 (7) ◽  
pp. 3454-3456 ◽  
Author(s):  
Martin J. Elhay ◽  
Thomas Oettinger ◽  
Peter Andersen
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Guinea Pig ◽  
Skin Test ◽  
Guinea Pigs ◽  
Delayed Type Hypersensitivity ◽  
C Terminus ◽  
Skin Responses ◽  
The Individual ◽  
New Skin

ABSTRACT Two antigens from Mycobacterium tuberculosis, ESAT-6 and MPT64, elicited delayed-type hypersensitivity (DTH) skin responses in outbred guinea pigs infected with M. tuberculosis by the aerosol and intravenous routes but not those sensitized with M. bovis BCG or M. avium. The DTH epitope of ESAT-6 was mapped to the C terminus. Nonresponders to the individual antigens were found, but all animals responded to a combination of ESAT-6 and MPT64 or their respective minimal target peptides. Correspondingly, these molecules could form the basis of a new skin test for tuberculosis.

scholarly journals Use of Mycobacterium tuberculosisComplex-Specific Antigen Cocktails for a Skin Test Specific for Tuberculosis

1998 ◽  
Vol 66 (8) ◽  
pp. 3606-3610 ◽  
Author(s):  
Konstantin Lyashchenko ◽  
Claudia Manca ◽  
Roberto Colangeli ◽  
Anna Heijbel ◽  
Alan Williams ◽  
...  
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Guinea Pigs ◽  
Nontuberculous Mycobacteria ◽  
Skin Testing ◽  
Specific Antigen ◽  
Diagnostic Value ◽  
Mycobacterial Species ◽  
Diagnostic Specificity ◽  
Single Antigen

ABSTRACT The tuberculin skin test currently used to diagnose infection withMycobacterium tuberculosis has poor diagnostic value, especially in geographic areas where the prevalence of tuberculosis is low or where the environmental burden of saprophytic, nontuberculous mycobacteria is high. Inaccuracy of the tuberculin skin test often reflects a low diagnostic specificity due to the presence in tuberculin of antigens shared by many mycobacterial species. Thus, a skin test specific for tuberculosis requires the development of new tuberculins consisting of antigens specific to M. tuberculosis. We have formulated cocktails of two to eight antigens of M. tuberculosis purified from recombinant Escherichia coli. Multiantigen cocktails were evaluated by skin testing guinea pigs sensitized with M. bovis BCG. Reactivity of multiantigen cocktails was greater than that of any single antigen. Cocktail activity increased with the number of antigens in the cocktail even when the same amount of total protein was used for cocktails and for each single antigen. A cocktail of four purified antigens specific for the M. tuberculosis complex elicited skin test responses only in BCG-immunized guinea pigs, not in control animals immunized with M. avium. These findings open the way to designing a multiantigen formulation for a skin test specific for tuberculosis.

scholarly journals Characterization of the Secreted MPT53 Antigen ofMycobacterium tuberculosis

2001 ◽  
Vol 69 (9) ◽  
pp. 5936-5939 ◽  
Author(s):  
Sadie Johnson ◽  
PierNatale Brusasca ◽  
Konstantin Lyashchenko ◽  
John S. Spencer ◽  
Harald G. Wiker ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Mycobacterium Avium ◽  
Specific Antibody ◽  
Nontuberculous Mycobacteria ◽  
Polyclonal Antibodies ◽  
Antibody Responses ◽  
Delayed Type Hypersensitivity ◽  
Secreted Protein

ABSTRACT MPT53 is a secreted protein of Mycobacterium tuberculosis. Southern transfer and hybridization showed mpt53 to be conserved in the M. tuberculosis complex and to have homology with DNA fromMycobacterium avium and other nontuberculous mycobacteria. However, anti-MPT53 polyclonal antibodies detected no antigen in the culture filtrates of M. avium and other nontuberculous mycobacteria. MPT53 of M. tuberculosisinduced strong, tuberculosis-specific antibody responses in guinea pigs but induced no delayed-type hypersensitivity. Involvement in immune responses during human tuberculosis was very modest.

scholarly journals Immune Responses to Defined Antigens of Mycobacterium bovis in Cattle Experimentally Infected with Mycobacterium kansasii

2006 ◽  
Vol 13 (6) ◽  
pp. 611-619 ◽  
Author(s):  
W. R. Waters ◽  
M. V. Palmer ◽  
T. C. Thacker ◽  
J. B. Payeur ◽  
N. B. Harris ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Bovine Tuberculosis ◽  
Nontuberculous Mycobacteria ◽  
Gamma Interferon ◽  
Delayed Type Hypersensitivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Antibodies ◽  
Specific Serum ◽  
Specific Proteins

ABSTRACT Cross-reactive responses elicited by exposure to nontuberculous mycobacteria often confound the interpretation of antemortem tests for Mycobacterium bovis infection of cattle. The use of specific proteins (e.g., ESAT-6, CFP-10, and MPB83), however, generally enhances the specificity of bovine tuberculosis tests. While genes for these proteins are absent from many nontuberculous mycobacteria, they are present in M. kansasii. Instillation of M. kansasii into the tonsillar crypts of calves elicited delayed-type hypersensitivity and in vitro gamma interferon and nitrite concentration responses of leukocytes to M. avium and M. bovis purified protein derivatives (PPDs). While the responses of M. kansasii-inoculated calves to M. avium and M. bovis PPDs were approximately equivalent, the responses of M. bovis-inoculated calves to M. bovis PPD exceeded their respective responses to M. avium PPD. The gamma interferon and nitrite responses of M. kansasii-inoculated calves to recombinant ESAT-6-CFP-10 (rESAT-6-CFP-10) exceeded corresponding responses of noninoculated calves as early as 15 and 30 days after inoculation, respectively, and persisted throughout the study. The gamma interferon and nitrite responses of M. bovis-inoculated calves to rESAT-6-CFP-10 exceeded the corresponding responses of M. kansasii-inoculated calves beginning 30 days after inoculation. By using a lipoarabinomannan-based enzyme-linked immunosorbent assay, specific serum antibodies were detected as early as 50 days after challenge with M. kansasii. By a multiantigen print immunoassay and immunoblotting, serum antibodies to MPB83, but not ESAT-6 or CFP-10, were detected in M. kansasii-inoculated calves; however, responses to MPB83 were notably weaker than those elicited by M. bovis infection. These findings indicate that M. kansasii infection of calves elicits specific responses that may confound the interpretation of bovine tuberculosis tests.

scholarly journals Generation of Attenuated Mycobacterium bovis Strains by Signature-Tagged Mutagenesis for Discovery of Novel Vaccine Candidates

2005 ◽  
Vol 73 (4) ◽  
pp. 2379-2386 ◽  
Author(s):  
Desmond M. Collins ◽  
Bronwyn Skou ◽  
Stefan White ◽  
Shalome Bassett ◽  
Lauren Collins ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Guinea Pigs ◽  
Essential Role ◽  
Immunoblot Analysis ◽  
Infection Model ◽  
Vaccine Candidates ◽  
Mouse Infection Model ◽  
Potential Vaccine

ABSTRACT Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex, has a particularly wide host range and causes tuberculosis in most mammals, including humans. A signature tag mutagenesis approach, which employed illegitimate recombination and infection of guinea pigs, was applied to M. bovis to discover genes important for virulence and to find potential vaccine candidates. Fifteen attenuated mutants were identified, four of which produced no lesions when inoculated separately into guinea pigs. One of these four mutants had nine deleted genes including mmpL4 and sigK and, in guinea pigs with aerosol challenge, provided protection against tuberculosis at least equal to that of M. bovis BCG. Seven mutants had mutations near the esxA (esat-6) locus, and immunoblot analysis of these confirmed the essential role of other genes at this locus in the secretion of EsxA (ESAT-6) and EsxB (CFP10). Mutations in the eight other attenuated mutants were widely spread through the chromosome and included pks1, which is naturally inactivated in clinical strains of M. tuberculosis. Many genes identified were different from those found by signature tag mutagenesis of M. tuberculosis by use of a mouse infection model and illustrate how the use of different approaches enables identification of a wider range of attenuating mutants.

scholarly journals Comparison of Two Commercially Available Gamma Interferon Blood Tests for Immunodiagnosis of Tuberculosis

2007 ◽  
Vol 15 (1) ◽  
pp. 168-171 ◽  
Author(s):  
Jose Domínguez ◽  
Juan Ruiz-Manzano ◽  
Malú De Souza-Galvão ◽  
Irene Latorre ◽  
Celia Milà ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
Mycobacterium Bovis ◽  
Latent Infection ◽  
Positive Tuberculin Skin Test ◽  
Gamma Interferon ◽  
Bcg Vaccination ◽  
Blood Tests

ABSTRACT We evaluated the T-SPOT.TB and Quantiferon-TB Gold In tube (QFN-G-IT) tests for diagnosing Mycobacterium tuberculosis infection. T-SPOT.TB was more sensitive than QFN-G-IT in diagnosing both active and latent infection. Both gamma interferon tests were unaffected by prior Mycobacterium bovis BCG vaccination. Among children who were not BCG vaccinated but had a positive tuberculin skin test, QFN-G-IT was negative in 53.3% of cases, and T-SPOT.TB was negative in 50% of cases.

scholarly journals Influence of Mycobacterium bovis BCG Vaccination on Cellular Immune Response of Guinea Pigs Challenged with Mycobacterium tuberculosis

2008 ◽  
Vol 15 (8) ◽  
pp. 1248-1258 ◽  
Author(s):  
Diane Ordway ◽  
Marcela Henao-Tamayo ◽  
Crystal Shanley ◽  
Erin E. Smith ◽  
Gopinath Palanisamy ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Guinea Pigs ◽  
Lung Damage ◽  
Cell Populations ◽  
Lung Pathology ◽  
Bcg Vaccination ◽  
Macrophage Populations ◽  
Cellular Immune

ABSTRACT Mycobacterium bovis bacillus Calmette-Guérin (BCG) currently remains the only licensed vaccine for the prevention of tuberculosis. In this study, we used a newly described flow cytometric technique to monitor changes in cell populations accumulating in the lungs and lymph nodes of naïve and vaccinated guinea pigs challenged by low-dose aerosol infection with virulent Mycobacterium tuberculosis. As anticipated, vaccinated guinea pigs controlled the growth of the challenge infection more efficiently than controls did. This early phase of bacterial control in immune animals was associated with increased accumulation of CD4 and CD8 T cells, including cells expressing the activation marker CD45, as well as macrophages expressing class II major histocompatibility complex molecules. As the infection continued, the numbers of T cells in the lungs of vaccinated animals waned, whereas the numbers of these cells expressing CD45 increased. Whereas BCG vaccination reduced the influx of heterophils (neutrophils) into the lungs, an early B-cell influx was observed in these vaccinated animals. Overall, vaccine protection was associated with reduced pathology and lung damage in the vaccinated animals. These data provide the first direct evidence that BCG vaccination accelerates the influx of protective T-cell and macrophage populations into the infected lungs, diminishes the accumulation of nonprotective cell populations, and reduces the severity of lung pathology.

Mycobacterium bovis BCG vaccination modulates TNF-α production after pulmonary challenge with virulent Mycobacterium tuberculosis in guinea pigs

Tuberculosis ◽  
2007 ◽  
Vol 87 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Toshiko Yamamoto ◽  
Todd M. Lasco ◽  
Kazuyuki Uchida ◽  
Yoshitaka Goto ◽  
Amminikutty Jeevan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Guinea Pigs ◽  
Mycobacterium Bovis Bcg ◽  
Bcg Vaccination ◽  
Tnf Α
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