Sleeping Beauty and the Story of the Bacille Calmette-Guérin Vaccine

Fletcher, Helen A.

doi:10.1128/mbio.01370-16

Cited by 12 publications

(8 citation statements)

References 17 publications

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“…While VPM1002 has progressed through the development pipeline, next-generation derivatives of this promising candidate have been developed and tested in pre-clinical studies, with the aim of further enhancing immunogenicity and/or safety ( 126 ). The most successful of these so far is VPM1002 ΔnuoG , which increased protection compared to its parental strain rBCG ΔureC : hly in mice while maintaining safety ( 96 ).…”

Section: Rbcgs Against Tbmentioning

confidence: 99%

Next-Generation Vaccines Based on Bacille Calmette–Guérin

2018

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Tuberculosis (TB), caused by the intracellular bacterium Mycobacterium tuberculosis (Mtb), remains a major health threat. A live, attenuated mycobacterium known as Bacille Calmette–Guérin (BCG), derived from the causative agent of cattle TB, Mycobacterium bovis, has been in clinical use as a vaccine for 90 years. The current incidence of TB demonstrates that BCG fails to protect sufficiently against pulmonary TB, the major disease manifestation and source of dissemination. The protective efficacy of BCG is on average 50% but varies substantially with geographical location and is poorer in those with previous exposure to mycobacteria. BCG can also cause adverse reactions in immunocompromised individuals. However, BCG has contributed to reduced infant TB mortality by protecting against extrapulmonary TB. In addition, BCG has been associated with reduced general childhood mortality by stimulating immune responses. In order to improve the efficacy of BCG, two major strategies have been employed. The first involves the development of recombinant live mycobacterial vaccines with improved efficacy and safety. The second strategy is to boost BCG with subunit vaccines containing Mtb antigens. This article reviews recombinant BCG strains that have been tested against TB in animal models. This includes BCG strains that have been engineered to induce increased immune responses by the insertion of genes for Mtb antigens, mammalian cytokines, or host resistance factors, the insertion of bacterial toxin-derived adjuvants, and the manipulation of bacterial genes in order to increase antigen presentation and immune activation. Subunit vaccines for boosting BCG are also briefly discussed.

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Section: Rbcgs Against Tbmentioning

confidence: 99%

Next-Generation Vaccines Based on Bacille Calmette–Guérin

2018

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“…We still need to understand why BCG gives such variable protection against pulmonary TB in different settings. The BCG vaccine remains critical for the development of new TB vaccines, many of which will be given as a booster vaccine after BCG vaccination, and any factors that affect how BCG works may also impact on these as well as on new genetically modified BCG vaccines or other live mycobacterial vaccines ( 2 , 3 ).…”

Section: Introductionmentioning

confidence: 99%

What Have We Learnt about BCG Vaccination in the Last 20 Years?

2017

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A number of new tuberculosis (TB) vaccines have been or are entering clinical trials, which include genetically modified mycobacteria, mycobacterial antigens delivered by viral vectors, or mycobacterial antigens in adjuvant. Some of these vaccines aim to replace the existing BCG vaccine but others will be given as a boosting vaccine following BCG vaccination given soon after birth. It is clear that the existing BCG vaccines provide incomplete and variable protection against pulmonary TB. This review will discuss what we have learnt over the last 20 years about how the BCG vaccine induces specific and non-specific immunity, what factors influence the immune responses induced by BCG, and progress toward identifying correlates of immunity against TB from BCG vaccination studies. There is still a lot to learn about the BCG vaccine and the insights gained can help the development of more protective vaccines.

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“…After good toleration was shown in Phase I clinical trials, Phase II is currently ongoing. 55,56 Finally, BCG effectiveness can be affected by antimicrobial peptides (AMPs) produced by mammalian cells to eliminate pathogens from the urinary tract. Cho et al produced recombinant BCGexpressing proteins that inhibit AMPs and lead to low survival of BC cells in vitro due to increased BCG internalization and cytokine secretion.…”

Section: Recombinant Bcgsmentioning

confidence: 99%

<p>Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update</p>

Guallar-Garrido

Julián

2020

ITT

142

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Physicians treating patients affected by nonmuscle-invasive bladder cancer (NMIBC) have been in shock during the last six years since manufacturing restrictions on the production of the first-option medicine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), have resulted in worldwide shortages. This shortage of BCG has led to a rethinking of the established treatment guidelines for the rationing of the administration of BCG. Some possible schedule modifications consist of a decrease in the length of maintenance treatment, a reduction in the dose of BCG in intravesical instillations or the use of different BCG substrains. All these strategies have been considered valuable in times of BCG shortage. In addition, the lack of availability of BCG has also led to the general recognition of the need to find new treatment options for these patients so that they are not dependent on a single treatment. Few alternatives are committed to definitively replacing BCG intravesical instillations, but several options are being evaluated to improve its efficacy or to combine it with other chemotherapeutic or immunotherapeutic options that can also improve its effect. In this article, we review the current state of the treatment with BCG in terms of all of the aforementioned aspects.

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Sleeping Beauty and the Story of the Bacille Calmette-Guérin Vaccine

Cited by 12 publications

References 17 publications

Next-Generation Vaccines Based on Bacille Calmette–Guérin

Next-Generation Vaccines Based on Bacille Calmette–Guérin

What Have We Learnt about BCG Vaccination in the Last 20 Years?

<p>Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update</p>

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