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Mycobacterium bovis-BCG vaccination induces a specific pulmonary transcriptome biosignature in mice

ABSTRACT: In the present study, we applied microarray technology to define a biosignature from the whole genome expression in lung and spleen samples after BCG vaccination and M. bovis infection of BALB/c mice. The aims were two-fold, namely to define biosignatures that could predict vaccine success before challenge, and biomarker patterns that correlated with anamnestic protective responses following exposure to virulent M. bovis. Further, Our aim was to define these markers to be detectable without in vitro antigenic challenge. After BCG vaccination, we defined a specific pulmonary gene expression signature related to the connective tissue development and function network that predicted vaccine success before M. bovis challenge. In addition, a Th17-related cytokine profile was found that correlated with vaccine-induced protective immunity following infection with virulent M. bovis in the lung as well as additional genes that were up-regulated in the spleens of vaccinated animals post-infection that was related to neutrophil biology and inflammation. This study has therefore prioritized both biomarkers predicting vaccination success before challenge and bio-signatures that are associated with protective immune responses that will be useful to evaluate future vaccine candidates.

ORGANISM(S): Mus musculus

PROVIDER: GSE21149 | GEO | 2010/06/28

SECONDARY ACCESSION(S): PRJNA126627

REPOSITORIES: GEO

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Mycobacterium bovis-BCG vaccination induces a specific pulmonary transcriptome biosignature in mice

Project description:In the present study, we applied microarray technology to define a biosignature from the whole genome expression in lung and spleen samples after BCG vaccination and M. bovis infection of BALB/c mice. The aims were two-fold, namely to define biosignatures that could predict vaccine success before challenge, and biomarker patterns that correlated with anamnestic protective responses following exposure to virulent M. bovis. Further, Our aim was to define these markers to be detectable without in vitro antigenic challenge. After BCG vaccination, we defined a specific pulmonary gene expression signature related to the connective tissue development and function network that predicted vaccine success before M. bovis challenge. In addition, a Th17-related cytokine profile was found that correlated with vaccine-induced protective immunity following infection with virulent M. bovis in the lung as well as additional genes that were up-regulated in the spleens of vaccinated animals post-infection that was related to neutrophil biology and inflammation. This study has therefore prioritized both biomarkers predicting vaccination success before challenge and bio-signatures that are associated with protective immune responses that will be useful to evaluate future vaccine candidates. Two groups of 20 mice each were immunised by a single intradermal injection of 2 x 10 to 5 CFU of M. bovis BCG (Vaccinated), or Hanks buffered salt solution (HBSS) (Unvaccinated). Six weeks later 5 mice from each group were euthanized for immunological analyses and the remaining mice from each group were challenged with approx 600 CFU M. bovis via the intranasal route. At days 3 and 14 post challenge five mice per group were euthanized and spleens and lungs harvested.

2010-07-29 | E-GEOD-21149 | biostudies-arrayexpress

Protective response to Brucella infection

Project description:Brucella ovis causes an important disease characterized by decreased fertility in rams, sporadic abortions in ewes and increased lamb mortality. The live attenuated B. melitensis Rev.1 vaccine is considered the best vaccine available against this infection. However, this vaccine shows variable protective efficacy ranging from 40% to 100%.The objective of this study was to identify possible correlates of protective response to B. ovis infection through the characterization by microarray hybridization and real-time RT-PCR of inflammatory and immune response genes upregulated in rams previously immunized with the B. melitensis Rev 1 vaccine strain and experimentally challenged with B. ovis. Gene expression profiles were compared before and after challenge with B. ovis between rams protected and those vaccinated but found infected after challenge. The genes upregulated in vaccinated and protected rams provide possible correlates of protective response to B. ovis infection in rams immunized with the B. melitensis Rev 1 vaccine. Gene expression profiles were compared before and after vaccination and challenge with B. ovis between rams protected with the B. melitensis Rev 1 vaccine strain and those vaccinated but infected after challenge. Total RNA was isolated from buffy coat samples before vaccination (T0), after vaccination and before challenge (T1) and 60 days post challenge (T2) using TriReagent (Sigma, St. Louis, MO, USA)

2010-06-25 | E-GEOD-13202 | biostudies-arrayexpress

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

Transcriptome analysis of a clinical phase Ia Mycobacterium bovis BCG vaccination study (sex and age matched European (Caucasian) males, 25-35 years, performed in Germany)

Project description:Global transcriptome analyses provide an excellent basis for the identification and definition of biomarkers with high relevance in infection processes, therapeutic intervention and protective immunity. The measurement applies three different state of the art transcriptomic technologies for global expression profiling to vaccine development. Different microarray platforms in conjunct to next generation sequencing (NGS) will build the basis for comparative approaches, such as up-down classification and correlation coefficients. This measurement is based on Agilent microarrays and a clinical trial phase Ia study with M. bovis BCG vaccination, using two different tuberculin skin test (PPD negative and PPD positive) groups. â?¢ Surrogate measurement using PBMCs â?¢ 4 time points: d0 (naÃ¯ve, pre-immunization) and d29, d57, d180 post m. bovis BCG immunization â?¢ Responses of PPD negative and PPD positive study groups â?¢ Group size of approximately 9 individuals European network of vaccine research and development (TRANSVAC) Microarray experiments were performed as single-color hybridizations using Agilent Technologies whole human genome 4x44K microarrays

2013-10-31 | E-GEOD-51059 | biostudies-arrayexpress

Transcriptome analysis of a clinical phase Ib Mycobacterium bovis BCG vaccination study (sex and age matched African males, 25-35 years, performed in South-Africa)

Project description:Global transcriptome analyses provide an excellent basis for the identification and definition of biomarkers with high relevance in infection processes, therapeutic intervention and protective immunity. The measurement applies three different state of the art transcriptomic technologies for global expression profiling to vaccine development. Different microarray platforms in conjunct to next generation sequencing (NGS) will build the basis for comparative approaches, such as up-down classification and correlation coefficients. This measurement is based on Agilent microarrays and a clinical trial phase Ib study with M. bovis BCG vaccination. M-bM-^@M-" Surrogate measurement using whole human blood M-bM-^@M-" 4 time points: d0 (naM-CM-/ve, pre-immunization) and d14, d28,d56, d168 post m. bovis BCG immunization M-bM-^@M-" Responses of PPD positive study groups M-bM-^@M-" Group size of approximately 6 individuals European network of vaccine research and development (TRANSVAC) Microarray experiments were performed as single-color hybridizations using Agilent Technologies whole human genome 4x44K microarrays

2013-10-31 | E-GEOD-51060 | biostudies-arrayexpress

Transcriptome analysis of a clinical phase Ib Mycobacterium bovis BCG vaccination study (sex and age matched African males, 25-35 years, performed in South-Africa)

Project description:Global transcriptome analyses provide an excellent basis for the identification and definition of biomarkers with high relevance in infection processes, therapeutic intervention and protective immunity. The measurement applies three different state of the art transcriptomic technologies for global expression profiling to vaccine development. Different microarray platforms in conjunct to next generation sequencing (NGS) will build the basis for comparative approaches, such as up-down classification and correlation coefficients. This measurement is based on Agilent microarrays and a clinical trial phase Ib study with M. bovis BCG vaccination. • Surrogate measurement using whole human blood • 4 time points: d0 (naïve, pre-immunization) and d14, d28,d56, d168 post m. bovis BCG immunization • Responses of PPD positive study groups • Group size of approximately 6 individuals European network of vaccine research and development (TRANSVAC)

2013-10-31 | GSE51060 | 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

Transcriptome analysis of non-human primate Chinese and Indian rhesus macaque spectrotype vaccination with Mycobacterium bovis BCG

Project description:Global transcriptome analyses provide an excellent basis for the identification and definition of biomarkers with high relevance in infection processes, therapeutic intervention and protective immunity. The measurement applies three different state of the art transcriptomic technologies for global expression profiling to vaccine development. Different microarray platforms in conjunct to next generation sequencing (NGS) will build the basis for comparative approaches, such as up-down classification and correlation coefficients. This measurement is based on Agilent microarrays and a pre-clinical study with M. bovis BCG vaccination, using two different non-human primate Chinese and Indian rhesus macaque spectrotypes. • Surrogate measurement using whole blood RNA • 7 time points: d-14 and d0 (naïve, pre-immunization) and d1, d3, d7, d21, d42 post M. bovis BCG immunization • Responses of two macaque spectrotypes • Group size of 6 animals European network of vaccine research and development (TRANSVAC)

2016-05-01 | GSE51061 | GEO

Transcriptome analysis of a clinical phase Ia Mycobacterium bovis BCG vaccination study (sex and age matched European (Caucasian) males, 25-35 years, performed in Germany)

Project description:Global transcriptome analyses provide an excellent basis for the identification and definition of biomarkers with high relevance in infection processes, therapeutic intervention and protective immunity. The measurement applies three different state of the art transcriptomic technologies for global expression profiling to vaccine development. Different microarray platforms in conjunct to next generation sequencing (NGS) will build the basis for comparative approaches, such as up-down classification and correlation coefficients. This measurement is based on Agilent microarrays and a clinical trial phase Ia study with M. bovis BCG vaccination, using two different tuberculin skin test (PPD negative and PPD positive) groups. • Surrogate measurement using PBMCs • 4 time points: d0 (naïve, pre-immunization) and d29, d57, d180 post m. bovis BCG immunization • Responses of PPD negative and PPD positive study groups • Group size of approximately 9 individuals European network of vaccine research and development (TRANSVAC)

2013-10-31 | GSE51059 | GEO

Transcriptional signature of BCG vaccination

Project description:The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity. Here, we investigated the BCG-specific gene expression changes induced in PBMCs and CD4 memory T cells by BCG in individuals pre- and 8m post vaccination. We also determined whether reactivity against a peptide pool defined in individuals with controlled latent TB infection (MTB300), and with peptides homologous to peptides found in BCG, was boosted following BCG vaccination.

2021-12-06 | GSE156422 | GEO

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