Tuberculosis II: the failure of the BCG vaccine

Maes, Roland

doi:10.1054/mehy.1997.0706

Cited by 8 publications

(3 citation statements)

References 40 publications

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“…Protection afforded by large-scale vaccination with Bacillus Calmette-Guerin (BCG) does not seem to provide a satisfactory answer to the problem of preventive medicine in mycobacterial diseases [11][12][13] . Previous studies performed by Stenger and colleagues showed that a virulent strain of M. tuberculosis is able to down-regulate severely the expression of CD1b molecule on human monocytes activated by GM-CSF 14 .…”

Section: Introductionmentioning

confidence: 99%

Bacillus Calmette-Guerin Down-Regulates CD1b Induction by Granulocyte-Macrophage Colony Stimulating Factor in Human Peripheral Blood Monocytes

Prete¹,

Giuliani²,

Iona³

et al. 2001

Journal of Chemotherapy

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Non-peptide antigens (e.g. glycolipids of microbial origin) presented by monocyte-associated CD1 molecules to T cells appear to play an important role in host immunity against tuberculosis and other pathogenic bacteria. Since vaccination with Bacillus Calmette-Guerin (BCG) has limited efficacy, the influence of viable BCG organisms on the induction of CD1b antigen by granulocyte macrophage-colony stimulating factor (GM-CSF) has been tested in adherent mononuclear cells obtained from peripheral blood of healthy donors. The results indicate that the vaccine reduces substantially CD1b induction by GM-CSF. On the other hand, BCG was found to promote a slight increase in the expression of this molecule on target cells not exposed to GM-CSF. Attempts to reverse the antagonistic effects of BCG on GM-CSF with high concentrations of GM-CSF, alone, or associated with IL-4, were unsuccessful. Moreover, mycobacteria suppression by 10 microg/ml of rifampin, did not affect BCG influence on CD1b induction. The present results suggest that mycobacterium-induced impairment of the CD1 system could play a role in the unsatisfactory results obtained with BCG vaccination.

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Section: Introductionmentioning

confidence: 99%

Bacillus Calmette-Guerin Down-Regulates CD1b Induction by Granulocyte-Macrophage Colony Stimulating Factor in Human Peripheral Blood Monocytes

Prete¹,

Giuliani²,

Iona³

et al. 2001

Journal of Chemotherapy

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“…Heterodox views should be evaluated on their merits and not excluded on sentimental grounds: bad news is not necessary false. If publications on humoral responses are given credit, evaluated properly and integrated [42][43][44][45][46], the following conclusions are drawn:…”

Section: Resultsmentioning

confidence: 99%

A Critical Appraisal of the Ban on Serological Tests for Tuberculosis Usefulness of Serological Monitoring of Tuberculosis Antibodies during the Treatment of TB Patients

Maes¹

2016

Clin Microbiol

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In 2011, the WHO banned the use of serological tests for the detection of antibodies against mycobacteria. This ban rests on a meta-analysis that observed a disparity in accuracy and specificity of results reported in various studies using this technique. All the included results were either level II observational studies or level III expert opinions. The immense majority of studies on other aspects of TB, as microscopy and vaccine efficacy, also pertain to these levels and present the same spread of results. The WHO policy statement rests on incorrect and invalid evidence. The experts analysed a pool of published studies of widely divergent quality, using different serological markers, and drew thereupon conclusions on quality of the serological test itself instead of on the quality of the studies analysed. In addition, the authors of the meta-analysis report results that are sometimes incorrect, drew conclusions on incomplete data, removed publications from their study using dubious reasons, lumped together results that should have been analysed separately and finally failed to take into consideration the value of the golden diagnostic methods used today. I intend to prove that serology is a very useful complementary tool in the diagnostic and prognostic of mycobacterial infections and that, had the WHO based their analysis on the complete information available, they would have supported the use of some serological tools for the diagnosis of TB instead of banning them.

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“…Its use was imposed worldwide in 1950 by the WHO. 13 It has been administered to 4 billion people ever since. Despite the addition of factors supposed to enhance the immunity produced by BCG, the vaccine has done little to contain the pandemic as it is ineffective once the individual is infected.…”

Section: The Bcg Vaccinementioning

confidence: 99%

Targeting Lsr2/DNA complexation for dysregulation of gene expression in Mycobacterium Tuberculosis

et al. 2013

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The identification of new drug targets and mechanisms of action against tuberculosis has become urgent, as the emergence of drug-resistant strains has made many treatments ineffective. Lsr2 is a protein encoded by the Mycobacterium tuberculosis genome that acts as a global repressor of transcription by binding AT-rich promoter regions of the mycobacterial DNA. Inhibiting this function could potentially dysregulate a wide array of genes, as Lsr2 binds about 20% of the Mycobacterium tuberculosis genome. Among them are key genes involved in mycobacterial virulence, cell wall biosynthesis or antibiotics-inducible genes that confer multi-drug tolerance. The structure of the DNA-binding C-terminal domain has been solved by nuclear magnetic resonance while the dimerization N-terminal domain was solved using X-ray crystallography, but there is no crystal structure of the full-length protein to this day.The first part of this work describes the development of a high-throughput assay that enabled the identification of Zafirlukast as an inhibitor of the Lsr2/DNA complexation. This ability was shown in vitro using a fluorescence polarization assay.Zafirlukast also exhibits growth inhibition of Mycobacterium smegmatis and Mycobacterium tuberculosis on a Kirby Bauer assay, but shows no activity against Dr. Donald R. Ronning, for all his guidance, kindness and patience throughout my thesis project. Thank you for teaching me so much and being such a great mentor. The experience I gained here has been the most instrumental one in my career development and perspectives. I will always be grateful.My appreciation extends to my committee members Dr. Max O. Funk and Dr. John J. Bellizzi as well as the whole Chemistry Department of the University of Toledo. I would also like to thank my fellow labmates for passing on their knowledge and being such a friendly team to work with. I spent a wonderful time here with all of you! I want to particularly acknowledge Vidhi for sharing a lot of lab skills when I began working in the lab and Dr. Jimmy Franco for helping me get started on this project. I must also thank my loving family and friends in France who have been amazingly supportive, especially my best friend Anne and my friend Mathilde.Finally, I want to thank my friends here for all the laughs and good times that have been my strength. I am particularly thankful for meeting Edma, Mathieu and Jared.Last but not least, a very special thanks goes to my great friend Quentin who shared most of this American adventure with me and was always there for me. vi

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Tuberculosis II: the failure of the BCG vaccine

Cited by 8 publications

References 40 publications

Bacillus Calmette-Guerin Down-Regulates CD1b Induction by Granulocyte-Macrophage Colony Stimulating Factor in Human Peripheral Blood Monocytes

Bacillus Calmette-Guerin Down-Regulates CD1b Induction by Granulocyte-Macrophage Colony Stimulating Factor in Human Peripheral Blood Monocytes

A Critical Appraisal of the Ban on Serological Tests for Tuberculosis Usefulness of Serological Monitoring of Tuberculosis Antibodies during the Treatment of TB Patients

Targeting Lsr2/DNA complexation for dysregulation of gene expression in Mycobacterium Tuberculosis

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