The tuberculosis vaccine challenge

Brennan, Michael J.

doi:10.1016/j.tube.2004.09.001

Cited by 39 publications

(25 citation statements)

References 29 publications

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“…The continuously falling efficacy of the BCG vaccine has generated intense research into development of novel vaccines to fight against TB, a disease that affects a third of the world's populations [1][2][3][4]. While examinations of newly developed attenuated virulent MTB and recombinant BCG strains have shown comparable efficacy with the current BCG vaccine, both involve use of live bacteria, with no comparative history of clinical safety [42][43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

“…The existing vaccine is an attenuated strain of Mycobacterium bovis Bacillus Calmette-Guerin (BCG), which, unfortunately, has varying levels of reported efficacy (0-80%). While many novel TB vaccines have been developed [4,5], few have demonstrated protective efficacy that can surpass BCG, which remains the only vaccine approved for human use. Previous research indicates that addition of adjuvant components to the BCG vaccine significantly enhances immune responses to promote host protection against subsequent challenge with virulent MTB [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Hwang¹,

Kruzel

Actor³

2009

Biochimie

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The current vaccine for tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an attenuated strain of Mycobacterium bovis bacillus Calmette-Guerin (BCG). BCG has proven to be effective in children, however, efficacy wanes in adulthood. Lactoferrin, a natural protein with immunomodulatory properties, is a potential adjuvant candidate to enhance efficacy of BCG. These studies define bovine lactoferrin as an enhancer of the BCG vaccine, functioning in part by modulating macrophage ability to present antigen and stimulate T-cells. BCG-infected bone marrow derived macrophages (BMMs) cultured with bovine lactoferrin increased the number of MHC II + expressing cells. Addition of IFN-γ and lactoferrin to BCG-infected BMMs enhanced MHC II expressiona dna increased the ratio of CD86/CD80. Lactoferrin treated BCG-infected BMMs were able to stimulate an increase in IFN-γ production from presensitized CD3 + splenocytes. Together, these results demonstrate that bovine lactoferrin is capable of modulating BCG-infected macrophages to enhance T-cell stimulation through increased surface expression of antigen presentation and costimulatory molecules, which potentially explains the observed in vivo bovine lactoferrin enhancement of BCG vaccine efficacy to protect against virulent MTB infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Hwang¹,

Kruzel

Actor³

2009

Biochimie

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“…In any case, none of these new vaccines was completely protective and capable of preventing infection. These results, coupled with the fact that BCG is effective in preventing the most severe forms of TB disease in infants, make the substitution of BCG with a new vaccine not feasible for ethical concerns [14]. For these reasons, an option that is being pursued aims to develop an improved version of BCG which could be administered in substitution of the currently available strain.…”

Section: Need For a New Vaccinementioning

confidence: 99%

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Morandi

Sali

Manganelli

et al. 2013

J Infect Dev Ctries

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The only vaccine available against tuberculosis (TB), the Bacille Calmette-Guerin (BCG), does not provide effective protection against the most common forms of adult TB and in recent years efforts have been made to develop a new and improved vaccine. Among the strategies implemented, the generation of a new live attenuated mycobacterial strain is seen as one of the most promising and feasible, for scientific, ethical and practical reasons. The new understanding of the biology of the tubercle bacilli and of host-pathogen interaction processes, coupled with the possibility to engineer BCG or M. tuberculosis, opened new avenues to design "intelligent" vaccines, capable of eliciting the immune response associated with protection while avoiding the induction of the host immune response associated with immunopathology. The complex and highly immunogenic mycobacterial cell wall can shape the general and antigen specific immune response elicited following immunization, and the possibility to exploit this knowledge may lead to the development of new vaccines that could help conquer this ancient human disease.

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“…The global incidence and prevalence of infection and multidrug resistance and the impact of AIDS and poverty diminish the likelihood that TB will be controlled without a more effective vaccine (9,15). Therefore, innovative approaches to discovering improved diagnostic methods, therapies, and vaccine candidates are very much needed.…”

mentioning

confidence: 99%

Mycobacterium tuberculosisBinding to Human Surfactant Proteins A and D, Fibronectin, and Small Airway Epithelial Cells under Shear Conditions

Hall-Stoodley

Watts²,

Crowther

et al. 2006

Infect Immun

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A crucial step in infection isTuberculosis (TB) remains a significant therapeutic challenge for the early 21st century. The global incidence and prevalence of infection and multidrug resistance and the impact of AIDS and poverty diminish the likelihood that TB will be controlled without a more effective vaccine (9, 15). Therefore, innovative approaches to discovering improved diagnostic methods, therapies, and vaccine candidates are very much needed.

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The tuberculosis vaccine challenge

Cited by 39 publications

References 29 publications

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Mycobacterium tuberculosisBinding to Human Surfactant Proteins A and D, Fibronectin, and Small Airway Epithelial Cells under Shear Conditions

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