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

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

PROVIDER: PRJNA876124 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21397969_1.fastq.gz	Fastqsanger.gz
	SRR21397969_2.fastq.gz	Fastqsanger.gz
	SRR21397970_1.fastq.gz	Fastqsanger.gz
	SRR21397970_2.fastq.gz	Fastqsanger.gz
	SRR21397971_1.fastq.gz	Fastqsanger.gz

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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.

2022-09-05 | GSE212586 | 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

Comparative transcriptomic analysis of THP‑1 derived macrophages infected with Mycobacterium tuberculosis H37Rv, H37Ra and BCG

Project description:In this study, RNA sequencing (Transcriptome sequencing) was employed to investigate the global transcriptome changes in the macrophages during the different strains of M.tb infection. THP-1 cells derived macrophages were exposed to the virulent M.tb strain H37Rv (Rv) or the avirulent M.tb strain H37Ra (Ra), and the M.tb BCG vaccine strain was used as a control. The cDNA libraries were prepared from M.tb infected macrophages and then sequenced.

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Stimulation with M.tb peptide pool induces multiple signaling pathways involved in providing protection during M.tb infection

Project description:M.tb Peptide pool induces an intricate network of signaling pathways in DCs and T cells which leads to enhanced cytokine production and T cell activation.

2021-01-06 | GSE164258 | GEO

Whole genome profiling of murine lymphocytes and statistical validation of a panel of immune molecules to predict vaccine efficacy against Mycobacterium tuberculosis

Project description:Transcriptional profiling of splenic lymphocytes derived from vaccinated mice, and ex-vivo exposed to M.tb.-infected macrophages in culture. Splenocytes from mice innoculated with Mycobacterium bovis BCG Pasteur (PAS), or M. bovis BCG Copenhagen (SSI), or heat killed BCG SSI (HK), or uninfected control, were ex vivo co-cultured with mouse bone marrow macrophages previously infected with M. tb.

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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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2021-11-30 | GSE179403 | GEO

BCG vaccination in rhesus macaques

Project description:BCG vaccination in rhesus macaques

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Transcriptional signature of BCG vaccination

Project description:Transcriptional signature of BCG vaccination

| PRJNA657864 | ENA

Stronger induction of trained immunity by mucosal BCG or MTBVAC vaccination

Project description:Vaccination against tuberculosis by intradermal Bacillus Calmette-Guérin (BCG) injection saves many lives, supposedly by inducing adaptive immune memory in lymphocytes. Epidemiologically, BCG vaccination is also associated with reduced childhood mortality unrelated to TB, which is attributed to innate immune memory, also termed trained immunity. We recently demonstrated improved protection against tuberculosis infection in highly susceptible rhesus macaques by mucosal BCG vaccination, correlating with a unique local but no peripheral immune profile. Here, we investigated local and peripheral innate immune function after intradermal versus mucosal vaccination with M. bovis BCG or the live attenuated, M. tuberculosis-derived candidate, MTBVAC. The results demonstrate an augmented frequency of trained immunity in monocytes after respiratory mucosal administration of live attenuated mycobacterial vaccines compared to intradermal immunization, with MTBVAC being equally potent as BCG. These results provide further support to strategies for improving TB vaccination and, more broadly, modulating innate immunity via mucosal surfaces.

2021-01-27 | GSE159046 | GEO

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