Unidentified
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB20047 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The BCG vaccine (Bacille Calmette-Guerin), only prophylactic measure against tuberculosis (TB), was obtained in the early twentieth century by Calmette and Guérin after 231 passages of a M. bovis clinical isolate in medium containing glycerin and bovine bile. Its protective efficacy against pulmonary TB in adults varies from 0-80% and the genetic differences among vaccines strains used worldwide contribute to this variation. The Brazilian vaccine strain, BCG Moreau, is considered a primitive strain and more immunogenic, closer to the original BCG when compared to newer strains, such as BCG Pasteur (reference strain). The characterization of BCG sub-strains can contribute not only to a better understanding of the vaccine and its protective effect, but also, in elucidating how different BCG culture conditions may contribute to the impact on the host's immune response. Thus, we aimed to characterize the differences in gene expression through the intracellular proteomic profile of BCG Moreau and Pasteur strains, cultivated in Sauton or 7H9 medium, using the methodology of two-dimensional electrophoresis (2DE) and mass spectrometry.
2025-10-23 | PXD030179 | Pride
Project description:New tuberculosis vaccines are highly desirable and urgently needed since the attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) provides only variable efficacy against the pulmonary form of the disease. The region of difference 1 (RD1), which is deleted in BCG and strongly impacts on Mycobacterium tuberculosis (Mtb) virulence and immunogenicity, represents a crucial locus to be engineered for either the improvement of the current BCG vaccine, or the attenuation of Mtb. Therefore, mutants secreting or not wild-type or mutated variants of the RD1-encoded 6 kDa early secreted antigenic target (ESAT-6) were generated. Comparative analysis of the transcriptome, phenotype, cytokine production profiles and the capacity to promote T cell responses were conducted in human primary dendritic cells (DCs), as they represent critical regulators of vaccine-induced immunity, unveiling a distinct immunogenic potential for BCG or Mtb mutants. In contrast to Mtb, BCG induced a poor DC maturation, and to our surprise, a BCG strain complemented with the RD1 region only partially restored DC maturation and expansion of interferon (IFN)-γ producing T cells. In contrast, infection with a recombinant attenuated Mtb strain, secreting a truncated version of ESAT-6 lacking 11 amino acids at the C-terminus portion, drove full maturation in infected DC and maintained their capacity to promote polarization of T helper (Th) 1 cells, as observed upon infection with the virulent Mtb. We performed a comparative microarray analysis of dendritic cells (DCs), infected with Mtb and BCG strains, expressing/complemented (MtbÎRD1::RD1 and BCG::RD1) or not (MtbÎRD1::B412 and BCG::B412) the/with the RD1 region. DCs were challenged with different BCG and Mtb recombinant strains for 8h.
2016-07-03 | E-GEOD-62423 | biostudies-arrayexpress
Project description:The current tuberculosis vaccine, Bacillus Calmette-Guérin (BCG), provides insufficient protection. We deleted the NADH dehydrogenase 1 subunit G (nuoG) gene from BCG ΔureC::hly, the most advanced live vaccine candidate in clinical development. Removal of nuoG enhanced co-localisation of LC3 to bacteria in human host cells. BCG ΔureC::hly ΔnuoG vaccination was safer than BCG and improved efficacy of BCG ΔureC::hly by reducing tuberculosis load in murine lungs 1000-fold.
2016-05-03 | GSE74282 | GEO
Project description:Tuberculosis (TB) is one of major causes of death worldwide. Bacillus Calmette-Guerin (BCG) is the only licensed TB vaccine and its inability to protect against adult pulmonary TB can be due to genetic differences among strains described since the 1940s. In this work, we compared the proteomic profile of the surface-associated proteins from M. bovis BCG Moreau, the Brazilian vaccine strain, and the BCG Pasteur reference strain. The methodology used was 2D-gel electrophoresis combined with mass spectrometry techniques (MALDI-TOF/TOF). We identified 115 proteins. Of these, 24 proteins showed differential expression between the two BCG strains. Furthermore, 27 proteins previously described as displaying moonlighting function were identified, 8 of these proteins showed variation in abundance comparing BCG Moreau to Pasteur and 2 of them presented two different domain hits.
2019-05-15 | PXD006141 | Pride
Project description:Tuberculosis (TB) is a serious public health concern in many regions of the world and the only approved vaccine to prevent TB is the live-attenuated BCG vaccine. Despite being widely used, the BCG vaccine fails to prevent pulmonary TB in adults. The BCG vaccine is administered during the neonatal period when levels of the immunosuppressive cytokine interleukin (IL)-27 are elevated, and previous studies have demonstrated that the source of IL-27 can impact downstream immune responses. We therefore sought to characterize the specific subpopulations of myeloid cells that produce IL-27 following BCG vaccination. To investigate this, we administered the BCG vaccine to neonatal IL-27p28eGFP mice that report IL-27 production. Our studies demonstrated that BCG vaccination steadily increased IL-27 production throughout the weeks post-vaccination. We also showed that a predominantly CD11b+ F4/80+population of IL-27 producers increased MHC class II expression following BCG vaccination in both the spleen and the lung. However, producers of IL-27 in these tissues differ, with a population of CD11c+ MHC II+ cells emerging in the spleen and a subset of Ly6G/C+ MHC II+ emerging in the lung. 10x scMultiome analysis further validated the increase in MHC class II expression and demonstrated improved antigen presentation functionality following vaccination. The sequencing analysis also revealed subpopulations of IL-27 producers with immunosuppressive functions such as a population of macrophages with increased Mrc1 expression post-vaccination. Our findings suggest that IL-27 producers are a heterogenous population of myeloid cells that impact the development of protective immune responses induced by the BCG vaccine.
2025-03-11 | GSE281538 | GEO
Project description:Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease that affects one-third of the world’s population. The sole extant vaccine for tuberculosis is the live attenuated Mycobacterium bovis bacille Calmette-Guerin (BCG). We examined 13 representative BCG strains from around the world to ascertain their ability to express DosR-regulated dormancy antigens. These are known to be recognized by T-cells of M. tuberculosis infected individuals, especially those harboring latent infections. Differences in expression of these antigens could be valuable for use as diagnostic markers to distinguish BCG vaccination from latent tuberculosis. We determined that all BCG strains were defective for induction of two dormancy genes, narK2 (Rv1737c) and narX (Rv1736c). NarK2 is known to be necessary for nitrate respiration during anaerobic dormancy. Analysis of the narK2/X promoter region revealed a base substitution mutation in all tested BCG strains and M. bovis in comparison to the M. tuberculosis sequence. We also show that nitrate reduction by BCG strains during dormancy was greatly reduced compared to M. tuberculosis and varied between tested strains. Several dormancy regulon transcriptional differences were also identified among the strains, as well as variation in their growth and survival. These findings demonstrate defects in DosR regulon expression during dormancy and phenotypic variation between commonly used BCG vaccine strains. Keywords: Comparison of induction of a subset of genes between various mycobacterial strains.
2008-05-03 | GSE11315 | GEO
Project description:Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease that affects one-third of the world’s population. The sole extant vaccine for tuberculosis is the live attenuated Mycobacterium bovis bacille Calmette-Guerin (BCG). We examined 13 representative BCG strains from around the world to ascertain their ability to express DosR-regulated dormancy antigens. These are known to be recognized by T-cells of M. tuberculosis infected individuals, especially those harboring latent infections. Differences in expression of these antigens could be valuable for use as diagnostic markers to distinguish BCG vaccination from latent tuberculosis. We determined that all BCG strains were defective for induction of two dormancy genes, narK2 (Rv1737c) and narX (Rv1736c). NarK2 is known to be necessary for nitrate respiration during anaerobic dormancy. Analysis of the narK2/X promoter region revealed a base substitution mutation in all tested BCG strains and M. bovis in comparison to the M. tuberculosis sequence. We also show that nitrate reduction by BCG strains during dormancy was greatly reduced compared to M. tuberculosis and varied between tested strains. Several dormancy regulon transcriptional differences were also identified among the strains, as well as variation in their growth and survival. These findings demonstrate defects in DosR regulon expression during dormancy and phenotypic variation between commonly used BCG vaccine strains. 12 different BCG strains were examined as well as M. tuberculosis H37Rv and M. bovis. Two arrays per strain were analyzed, one with the addition of nitric oxide and the other utilizing hypoxia treatment, both conditions shown to induce expression of the dormancy regulon. The reference sample for each array was log phase M. tuberculosis H37Rv.
2008-05-03 | E-GEOD-11315 | biostudies-arrayexpress
Project description:Currently, the only available vaccine against tuberculosis is Mycobacterium bovis Bacille Calmette-Guérin (BCG). Pulmonary tuberculosis protection provided by the vaccine varies depending on the strain, the patient’s age, and the evaluated population. Although the adaptive immune responses induced by different BCG strains have been widely studied, little conclusive data is available regarding innate immune responses, especially in macrophages. Here, we aimed to characterize the innate immune responses of human THP-1-derived macrophages at the transcriptional level following a challenge with either the BCG Mexico or Phipps strains. After a brief in vitro characterization of the bacterial strains and the innate immune responses, including nitric oxide production and cytokine profiles, we analyzed the mRNA expression patterns and performed pathway enrichment analysis using RNA microarrays. Our results showed that multiple biological processes were enriched, especially those associated with innate inflammatory and antimicrobial responses, including tumor necrosis factor (TNF)-α, type I interferon (IFN), and IFN-. These findings indicated the pro-inflammatory stimulation of macrophages induced by both BCG strains, at the cytokine level and in terms of gene expression. Our results demonstrated that both strains activated the innate immune response, with better modulation induced by BCG Phipps.
2022-04-10 | GSE171961 | GEO
Project description:Bacille Calmette Guerin (BCG) is the most widely administered vaccine in the world yet its mechanism of action remains unclear. In this study, we have used samples from a human mycobacterial challenge study in which previously BCG-vaccinated or BCG-naïve UK adults were challenged intradermally with a standard dose of BCG vaccine. BCG remaining at the site of vaccination was quantified by polymerase chain reaction from a skin biopsy sample taken two weeks post-challenge and was used as a measure of BCG growth and functional anti-mycobacterial immunity. Using gene expression microarrays and flow cytometric analysis of intracellular cytokine production, we show that the magnitude of the immune response is greater in previously vaccinated volunteers and that this correlates with reduced mycobacterial growth but increased scarring at the vaccination site. In particular the IFNγ and IL-17 pathways are strongly induced in previously vaccinated volunteers and correlate with reduced mycobacterial growth in this population. This study supports the use of BCG challenge as a tool for evaluating vaccine efficacy and identifying mechanisms of anti-mycobacterial immunity
2014-12-01 | GSE58636 | GEO
Project description:The reason for the largely variable protective effect against TB of the vaccine Bacille Calmette-Guerin (BCG) is not understood. In this study, we investigated whether epigenetic mechanisms are involved in the response of immune cells to the BCG vaccine. We isolated peripheral blood mononuclear cells (PBMCs) from BCG-vaccinated subjects and performed global DNA methylation analysis in combination with functional assays representative of innate immunity against Mycobacterium tuberculosis infection. Enhanced containment of replication was observed in monocyte-derived macrophages from a sub-group of BCG-vaccinated individuals (identified as ‘responders’). A stable and robust differential DNA methylation pattern in response to BCG could be observed in PBMCs isolated from the responders but not from the non-responders. Gene ontology analysis revealed that promoters with altered DNA methylation pattern were strongly enriched among genes belonging to immune pathways in responders, however no enrichments could be observed in the non-responders. Our findings suggest that BCG-induced epigenetic reprogramming of immune cell function can enhance anti-mycobacterial immunity. Understanding why BCG induces this responses in responders but not in nnon-responders could provide clues to improvement of TB vaccine efficacy.
2017-09-27 | GSE104287 | GEO