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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The innate and adaptive immune response to BCG stimulation in splenocytes taken from C57BL/6 mice

ABSTRACT: The aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from naïve and BCG vaccinated mice. The differences between naïve and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals. Splenocytes from 4 naïve and 4 BCG vaccinated female C57bl/6 mice were cultured for 12 hours with BCG (MOI 1:1) or without (unstimulated control). Each animal had a stimulated and an unstimulated sample hybridised to a beadchip.

ORGANISM(S): Mus musculus

SUBMITTER: leanne marsay

PROVIDER: E-GEOD-42090 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb).

Marsay Leanne L Matsumiya Magali M Tanner Rachel R Poyntz Hazel H Griffiths Kristin L KL Stylianou Elena E Marsh Philip D PD Williams Ann A Sharpe Sally S Fletcher Helen H McShane Helen H

Tuberculosis (Edinburgh, Scotland) 20130531 5

Development of an improved vaccine against tuberculosis (TB) is hindered by the lack of a surrogate of protection. Efficacy of new TB vaccines in humans can only be evaluated by expensive and time consuming efficacy trials within TB endemic areas. It is critical that vaccines with the greatest potential to protect are selected for these trials. Mycobacterial growth inhibition assays (MGIAs) have been developed with the hope that these in-vitro functional assays will correlate with protection, wh ...[more]

PMID: 23726784

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The innate and adaptive immune response to BCG stimulation in splenocytes taken from C57BL/6 mice

Project description:The aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from naïve and BCG vaccinated mice. The differences between naïve and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals.

2013-06-01 | GSE42090 | GEO

PBMC expression profiles of BCG vaccine protected infants and of BCG vaccinated infants who develop tuberculosis disease

Project description:Analysis of PBMC from 10 week old infants vaccinated with BCG at birth. During follow-up 26 infants developed tuberculosis (TB) (non-protected by BCG) and 20 infants did not develop TB despite documented exposure (protected by BCG). PBMC were stimulated with media only or reconstituted BCG for 4 and 12 hours. Results provide insight into the mechanisms behind the failure of BCG to protect against disease.

2014-06-30 | GSE20716 | GEO

Expression data from CD4+ splenocytes 6h post-sepsis

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Transcriptomic blood responses to mycobacteria in a BCG challenge model

Project description:Cattle were vaccinated at week 0 with the live attenuated M. bovis BCG SSI vaccine strain; some animals remain as non-vaccinated controls. After eight weeks animals were challenged intranodally with 108 BCG Tokyo cfu. Lymph nodes were harvested at week 11 and bacterial load in lymph nodes evaluated. Some BCG vaccinates had bacterial loads similar to those found in non-vaccinated animals (not-protected) and some animals had lower bacterial loads (protected) than non-vaccinated animals. Immune responses to mycobacteria were monitored in vitro by stimulation of whole blood with medium, purified protein derivative from M. bovis (PPD-B) or live BCG Tokyo longitudinally. Blood samples from 6 BCG-protected, 6 BCG-not-protected and 6 not-vaccinated. Challenged cattle stimulated with mycobacterial antigens or not were used to prepare RNA for RNAseq analysis at weeks 0 (vaccination), 8 (challenge), 9, 10 and 11. The outcome of this project would help not only in the selection of vaccine candidates but would also inform on the formulation of novel vaccines/vaccination strategies.

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Gene expression and cytokine profile correlate with mycobacterial growth in a human BCG challenge model

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

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MicroRNA expression profiling of PPD stimulated bovine PBMC from M. bovis-challenged control and BCG vaccinated cattle

Project description:Micro RNA profiling was performed on in vitro PPDB and nil stimulated bovine PBMCs isolated from BCG vaccinated and unvaccinated cattle before and after challenge with M. bovis.

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RNA-Seq of mouse lung vaccinated with subcutaneous BCG and two novel tuberculosis mucosal boosting nanovaccines

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2021-01-28 | E-MTAB-9449 | biostudies-arrayexpress

BCG vaccination of mice elicits transcriptional changes in blood that predict protection against M.tb. challenge

Project description:Although BCG has been used for almost 100 years to immunize against Mycobacterium tuberculosis, TB remains a global public health threat. Numerous clinical trials are underway studying novel vaccine candidates and strategies to improve or replace BCG, but vaccine development still lacks a well-defined set of immune correlates to predict vaccine-induced protection against tuberculosis. This study aimed to address this gap by examining transcriptional responses to BCG vaccination in C57BL/6 inbred mice, coupled with protection studies using Diversity Outbred mice. We evaluated relative gene expression in blood obtained from vaccinated mice, because blood is easily accessible and data can be translated to human studies. We first determined that the average peak time after vaccination is 14 days for gene expression of a small subset of immune-related genes in inbred mice. We then performed global transcriptomic analyses using whole blood samples obtained two weeks after mice were vaccinated with BCG. Using comparative bioinformatic analyses and qRT-PCR validation, we developed a working correlate panel of 18 genes that were highly correlated with administration of BCG but not heat-killed BCG. We then tested this gene panel using BCG-vaccinated Diversity Outbred mice and revealed associations between the expression of a subset of genes and disease outcomes after aerosol challenge with M. tuberculosis. These data therefore demonstrate that blood-based transcriptional immune correlates measured within a few weeks after vaccination can be derived to predict protection against M. tuberculosis, even in outbred populations.

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Human peripheral blood mononuclear cells stimulated in vitro by BCG strains or PPD

Project description:This experiment explored the transcriptional response of human peripheral blood mononuclear cells (PBMC) isolated from BCG-vaccinated individuals following 6 days of in vitro stimulation with 2x10^5 cfu of different Bacillus Calmette-Guérin (BCG) strains or 100 ng/ml Mycobacterium tuberculosis-derived purified protein derivative (PPD). The BCG strains used were BCG Russia (Russian BCG-I sub-strain), BCG Japan (Tokyo 172 sub-strain), BCG Denmark (Danish 1331 sub-strain) & BCG Pasteur.

2022-01-26 | E-MTAB-11345 | biostudies-arrayexpress

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