Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE212586 | GEO | 2022/09/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Gene expression analysis of peripheral blood mononuclear cells prior to and following vaccination of human volunteers with the novel TB vaccine candidate MVA85A

Project description:A greater understanding of the relationships between a vaccine, the immune response it induces, and protection from disease would greatly facilitate vaccine development. Modified Vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis (TB) vaccine designed to enhance responses induced by Bacille Calmette-Guerin (BCG). Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A and peaks one week post-vaccination, however, the variability in response between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression following vaccination with MVA85A and understand how these are related to long-term immunogenicity. 24 volunteers were vaccinated with 10^8 pfu MVA85A. 12 volunteers were vaccinated intramuscularly and 12 intradermally. Volunteers were healthy and did not have HIV, HCV, HBV or latent or active tuberculosis. Blood for this study was taken on the day of vaccination, immediately prior to the vaccine being given (day 0), and 2 and 7 days post-vaccination. Volunteers with a prior BCG vaccination were vaccinated with 1x10^8 pfu MVA85A either intradermally (id) or intramuscularly (im). Blood was taken immediately prior to vaccination (day 0) and 2 and 7 days post-vaccination. PBMCs were separated and frozen down. PBMCs were then thawed and RNA was extracted directly for microarray analysis. Some arrays contain control samples: from volunteers, incubated with either media alone or antigen 85, MVA85A or MVA wild type. These samples were used separately.

2012-09-28 | E-GEOD-40719 | biostudies-arrayexpress

Blood transcriptome following intravenous BCG vaccination in rhesus macaques

Project description:To determine the blood transcriptional response to intravenous (IV) BCG vaccination in rhesus macaques and identify correlates of vaccine-mediated protection against Mycobacterium tuberculosis (Mtb) challenge.

2023-06-19 | GSE218270 | GEO

Gene expression analysis of peripheral blood mononuclear cells prior to and following vaccination of human volunteers with the novel TB vaccine candidate MVA85A

2012-09-28 | GSE40719 | GEO

Blood transcriptome following BCG vaccination administered via different routes in rhesus macaques

Project description:To determine the blood transcriptional response to BCG vaccination administered via different routes in rhesus macaques and identify correlates of vaccine-mediated protection against Mycobacterium tuberculosis (Mtb) challenge.

2023-06-19 | GSE218157 | GEO

Mucosal exposure to non-tuberculous mycobacteria elicits B-cell mediated protection against pulmonary tuberculosis

Project description:Bacille Calmette Guerin (BCG) is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) disease. However, BCG has limited efficacy, necessitating the development of better vaccines. Non-tuberculous mycobacteria (NTM), a distinct lineage from Mtb, are opportunistic pathogens present in the environment. TB endemic countries experience higher exposure to NTM, but previous studies have not elucidated the relationship between NTM exposure and BCG efficacy. Therefore, we developed a mouse model (BCG+NTM) that mimics human BCG vaccination at an early stage and continuous NTM exposure via the oral route, including during TB infection. Our results show that BCG+NTM mice had improved protection against pulmonary TB correlating with increased pulmonary influx of B-cells, higher titers of anti-Mtb IgA and IgG antibodies in serum and airways, compared to mice vaccinated with BCG alone. Notably, the lungs of BCG+NTM mice developed B-cell aggregates expressing markers of germinal center formation as determined by spatial transcriptomics. We conclude a direct correlation between NTM exposure and protection from TB, with B-cells playing a crucial role.

2022-10-23 | GSE203037 | GEO

Defining Gene Signatures for Protective Immunity to Tuberculosis in the Chinese Cynomolgus Macaque Model

Project description:Gene expression profiles in PPD-stimulated and unstimulated peripherhal blood mononuclear cells isolated from chinese cynomolgus macaques before and after BCG vaccination and before and after M. tuberculosis challenge were compared in animals able to control TB infection and those that developed TB disease in order to identify potential correlates of protection and/or biomarkers of disease. 6 macaques received BCG vaccination prior to challenge and were able to control TB infection (vaccinated controllers). 3 unvaccinated macaques were also able to control TB infection after challenge (unvaccinated controllers) and 3 other unvaccinated macaques developed TB disease and reached humane endpoint criteria (unvaccinated progressors). PBMCs isolated at 8 and 18 weeks post BCG-vaccination from the vaccinated controllers and at 6 weeks post M.tb challenge and at 2 time-points when the animals were naive in all animals were stimulated with PPD. RNA was extracted from the cells and hybridised to and Agilent rhesus macaque GE microarray in a one-colour hybridisation. Gene expression post-vaccination and/or post-challenge was compared with expression before vaccination/challenge when the animals were naive.

2012-11-15 | E-GEOD-42273 | biostudies-arrayexpress

Deletion of nuoG in recombinant BCG vaccine against TB

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

BCG induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-y mediated trained immunity

Project description:After a century of the Bacillus Calmette-Guérin (BCG) vaccine, our understanding of its protection against homologous (Mycobacterium tuberculosis) or heterologous (e.g. influenza virus) infections is still limited. Here we show that systemic (intravenous) BCG vaccination (BCG-iv) provides significant protection against subsequent influenza A virus (IAV) infection in mice. We further demonstrate that the BCG-mediated cross-protection against IAV is largely due to the enrichment of conventional CD4+ αβ effector memory T cells that express high levels of CX3CR1hi in circulation trafficking into the lung parenchyma. Importantly, pulmonary CX3CR1hi T cells limit early viral infection in an antigen-independent manner via potent IFNγ production, which subsequently enhances long-term antimicrobial activity of the innate immune system like alveolar macrophages. Similarly, we uncover a prominent IFNγ signature in which its increased basal production was associated with enhanced BCG-mediated heterologous innate memory responses in BCG-vaccinated humans. These results offer insight into the unknown mechanism by which BCG has persistently displayed broad protection against non-tuberculous infections via a crosstalk between adaptive and innate memory responses.

2023-11-01 | GSE246201 | GEO

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.

2018-07-30 | GSE84867 | GEO

Comparison of M. tuberculosis and M. bovis BCG in diluted whole blood cultures

Project description:Despite wide scale vaccination with Mycobacterium bovis BCG, the prevalence of tuberculosis remains high, reflecting the global variable efficacy of this vaccine against adult pulmonary TB. Characterisation of different immune responses to M. tuberculosis and M. bovis BCG would increase understanding of pathology following M. tuberculosis infection or reactivation, and would facilitate the rational design of a new vaccine. Gene expression profiling was conducted on samples from diluted whole blood cultures from three healthy donors following incubation with live mycobacteria for six days. Approximately 8,000 gene entities were at least two-fold up- or down- regulated by the mycobacteria, and both mycobacteria induced similar expression changes in approximately 2,300 genes. Strikingly, many genes exhibited qualitatively different expression patterns, with over 1,000 genes up-regulated in response to M. bovis BCG but not changed by M. tuberculosis. Gene Ontology analysis revealed that the genes which failed to upregulate in M. tuberculosis-infected cultures included a large proportion of genes with lysosomal function. The inhibited up-regulation of expression of IFN-γ-inducible protein 30, acid phosphatase 2, cathepsin B and GM2 ganglioside activator was verified in samples from six biologically independent donors by qRT-PCR. The failure to up-regulate these genes in response to M. tuberculosis may constitute an immune evasion mechanism, preventing intracellular killing and antigen presentation. Blood from three healthy BCG-vaccinated donors was diluted with growth medium and incubated alone or with live M. tuberculosis (H37Rv), M. bovis BCG for 6 days. RNA samples were pooled before hybridisation.

2015-09-10 | E-GEOD-45386 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data