Assessment of BCG and inactivated Mycobacterium bovis vaccines in an experimental tuberculosis infection model in sheep

The effectiveness of an aerosol producing system (In-Tox Products, Albuquerque, NM) commonly used for toxicological studies of chemicals and radioisotopes was evaluated for experimental tuberculosis infection of mice. Previously, experimental tuberculosis of rodents has been accomplished by aerosol infection devices which exposed the entire animal to the aerosol within a chamber. We utilized the In-Tox system to infect animals via the respiratory route with Mycobacterium bovis strain Bacille Calmette-Guerin (BCG) as a model for experimental pulmonary tuberculosis. The advantage of the device tested is that exposure to the infectious aerosol is limited to the nose of the animal. The present instrument was found to yield good implantation of mycobacteria into the lungs. The infectious load was reproducible and, with the addition of some filtration, the infectious agent was well contained within the device. Our results showed that this device is easy to operate, produces an effective experimental aerosol infection and is safe for the investigator.

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Prior Exposure to Live Mycobacterium bovis BCG Decreases Cryptococcus neoformans-Induced Lung Eosinophilia in a Gamma Interferon-Dependent Manner

Infection and Immunity ◽

10.1128/iai.71.6.3384-3391.2003 ◽

2003 ◽

Vol 71 (6) ◽

pp. 3384-3391 ◽

Cited By ~ 19

Author(s):

Gerhard Walzl ◽

Ian R. Humphreys ◽

Ben G. Marshall ◽

Lorna Edwards ◽

Peter J. M. Openshaw ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Mycobacterium Bovis ◽

Mycobacterial Infection ◽

Gamma Interferon ◽

Delayed Type Hypersensitivity ◽

Infection Model ◽

Dependent Manner ◽

Interleukin 5 ◽

Lung Eosinophilia ◽

Mycobacterial Antigens

ABSTRACT Some common childhood infections appear to prevent the development of atopy and asthma. In some Mycobacterium bovis BCG-vaccinated populations, strong delayed-type hypersensitivity responses to mycobacterial antigens are associated with a reduced risk of atopy. Although BCG exposure decreases allergen-induced lung eosinophilia in animal models, little attention has been given to the effect of immunity to BCG on responses against live pathogens. We used the murine Cryptococcus neoformans infection model to investigate whether prior BCG infection can alter such responses. The present study shows that persistent pulmonary BCG infection of C57BL/6 mice induced an increase in gamma interferon, a reduction in interleukin-5, and a decrease in lung eosinophilia during subsequent Cryptococcus infection. This effect was long lasting, depended on the presence of live bacteria, and required persistence of mycobacterial infection in the lung. Reduction of eosinophilia was less prominent after infection with a mutant BCG strain (ΔhspR), which was rapidly cleared from the lungs. These observations have important implications for the development of vaccines designed to prevent Th2-mediated disease and indicate that prior lung BCG vaccination can alter the pattern of subsequent host inflammation.

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Experimental tuberculosis in the European badger (Meles meles) after endobronchial inoculation with Mycobacterium bovis: II. Progression of infection

Research in Veterinary Science ◽

10.1016/j.rvsc.2008.03.003 ◽

2008 ◽

Vol 85 (3) ◽

pp. 481-490 ◽

Cited By ~ 21

Author(s):

L.A.L. Corner ◽

E. Costello ◽

S. Lesellier ◽

D. O’Meara ◽

E. Gormley

Keyword(s):

Mycobacterium Bovis ◽

Meles Meles ◽

Experimental Tuberculosis ◽

European Badger

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

Infection and Immunity ◽

10.1128/iai.73.4.2379-2386.2005 ◽

2005 ◽

Vol 73 (4) ◽

pp. 2379-2386 ◽

Cited By ~ 20

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.

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Diagnosis of Mycobacterium bovis infection in livestock using gamma interferon assay and single intradermal comparative tuberculin test in Assam and Meghalaya

Indian Journal of Animal Research ◽

10.18805/ijar.v0iof.7662 ◽

2017 ◽

Author(s):

Acheenta G. Barua ◽

Himangshu Raj ◽

Ashok Kumar ◽

Chandana C. Barua ◽

Arundhati Purkayastha ◽

...

Keyword(s):

Mycobacterium Bovis ◽

Bovine Tuberculosis ◽

Screening Method ◽

Tuberculin Test ◽

Gamma Interferon ◽

Tuberculosis Infection ◽

Specific Detection ◽

Biochemical Tests ◽

Diagnostic Potential ◽

Pcr Targeting

The present study was carried out to investigate the diagnostic potential of gamma interferon (IFN-ã) assay and single intradermal comparative tuberculin test (SICTT), including species specification of bovine tuberculosis infection in different livestock farms of Assam and Meghalaya. A total of 199 animals (cattle and buffalo) were examined for bovine tuberculosis symptoms and swab samples were cultured. Biochemical tests and PCR were used for species specification of bovine tuberculosis. Out of 199 cases examined, 33 (16.58%) showed positive for SICTT, 39 (19.59%) for IFN-ã and 35(17.59%) for PCR. Based on PCR targeting pncA region, the confirmation was done for M. Bovis. IFN-ã thus ensures a sensitive and specific detection of early bovine tuberculosis infection together with SICTT and hence may be considered as a screening method of choice.

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Effects of Mycobacterium bovis on monocyte-derived macrophages from bovine tuberculosis infection and healthy cattle

FEMS Microbiology Letters ◽

10.1111/j.1574-6968.2011.02304.x ◽

2011 ◽

Vol 321 (1) ◽

pp. 30-36 ◽

Cited By ~ 12

Author(s):

Yang Wang ◽

Xiangmei Zhou ◽

Jingjun Lin ◽

Fei Yin ◽

Lihua Xu ◽

...

Keyword(s):

Mycobacterium Bovis ◽

Bovine Tuberculosis ◽

Tuberculosis Infection ◽

Healthy Cattle

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Increased Numbers of ESAT-6- and Purified Protein Derivative-Specific Gamma Interferon-Producing Cells in Subclinical and Active Tuberculosis Infection

Infection and Immunity ◽

10.1128/iai.68.10.6073-6076.2000 ◽

2000 ◽

Vol 68 (10) ◽

pp. 6073-6076 ◽

Cited By ~ 52

Author(s):

Timo Ulrichs ◽

Peter Anding ◽

Steven Porcelli ◽

Stefan H. E. Kaufmann ◽

Martin E. Munk

Keyword(s):

Mycobacterium Bovis ◽

Synthetic Peptides ◽

Gamma Interferon ◽

Active Tuberculosis ◽

Tuberculosis Infection ◽

Potential Candidate ◽

Tuberculosis Patients ◽

Purified Protein Derivative ◽

Healthy Donors ◽

Ifn Γ

ABSTRACT Numbers of gamma interferon (IFN-γ)-producing cells reactive to ESAT-6 antigen were increased in recent converters to purified protein derivative positivity and in tuberculosis patients but not in unvaccinated or Mycobacterium bovis BCG-vaccinated healthy donors. ESAT-6-reactive IFN-γ-producing cells in recent converters and tuberculosis patients recognized similar synthetic peptides. Thus, ESAT-6 is a potential candidate for use in detection of early, as well as active, tuberculosis and for control of the disease.

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Experimental tuberculosis in the European badger (Meles meles) after endobronchial inoculation of Mycobacterium bovis: I. Pathology and bacteriology

Research in Veterinary Science ◽

10.1016/j.rvsc.2006.10.016 ◽

2007 ◽

Vol 83 (1) ◽

pp. 53-62 ◽

Cited By ~ 44

Author(s):

L.A.L. Corner ◽

E. Costello ◽

S. Lesellier ◽

D. O’Meara ◽

D.P. Sleeman ◽

...

Keyword(s):

Mycobacterium Bovis ◽

Meles Meles ◽

Experimental Tuberculosis ◽

European Badger

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Enhanced Detection of Mycobacterium bovis-Specific T Cells in Experimentally-Infected Cattle

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.676710 ◽

2021 ◽

Vol 8 ◽

Author(s):

Paola M. Boggiatto ◽

Carly R. Kanipe ◽

Mitchell V. Palmer

Keyword(s):

T Cells ◽

Mycobacterium Bovis ◽

Cellular Response ◽

Γδ T Cells ◽

T Cell Response ◽

Health Concern ◽

Diagnostic Tools ◽

Infection Model ◽

Cell Mediated Immunity

Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to be a major economic burden associated with production losses and a public health concern due to its zoonotic nature. As with other intracellular pathogens, cell-mediated immunity plays an important role in the control of infection. Characterization of such responses is important for understanding the immune status of the host, and to identify mechanisms of protective immunity or immunopathology. This type of information can be important in the development of vaccination strategies, diagnostic assays, and in predicting protection or disease progression. However, the frequency of circulating M. bovis-specific T cells are often low, making the analysis of such responses difficult. As previously demonstrated in a different cattle infection model, antigenic expansion allows us to increase the frequency of antigen-specific T cells. Moreover, the concurrent assessment of cytokine production and proliferation provides a deeper understanding of the functional nature of these cells. The work presented here, analyzes the T cell response following experimental M. bovis infection in cattle via in vitro antigenic expansion and re-stimulation to characterize antigen-specific CD4, CD8, and γδ T cells and their functional phenotype, shedding light on the variable functional ability of these cells. Data gathered from these studies can help us better understand the cellular response to M. bovis infection and develop improved vaccines and diagnostic tools.

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