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GSE102459
Homo sapiens
161 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Systems biology has the potential to identify gene signatures associated with vaccine immunogenicity or protective efficacy. The main objective of our study was to identify optimal post-vaccination time points for evaluating blood RNA-expression profiles in recipients of the candidate tuberculosis vaccine M72/AS01. In this phase II open-label study (NCT01669096), healthy Bacillus Calmette-Gurin (BCG)-primed, HIV-negative adults were administered two doses (30-days apart) of M72/AS01. Blood samples were collected pre-dose 1, pre-dose 2 and 1, 7, 10, 14, 17 and 30 days post-dose 2. RNA expression in blood and peripheral-blood mononuclear cells (PBMCs) was quantified using microarray technology. The data analysis used as a reference, a PBMC-gene signature that was associated with the protective efficacy of a similarly adjuvanted candidate malaria vaccine. Peripheral-blood CD4+ T-cell reactivity, serum interferon-gamma (IFNG) concentrations and safety were also assessed. Twenty subjects completed the study and 18 subjects received two doses. The observed safety profile was similar to previous trials. Serum IFNG responses and M72-specific CD4+ T cell responses to vaccination were detected as expected, based on previous trial experience. PBMC and whole-blood RNA-expression data at day 14 post-dose 2 relative to pre-vaccination and whole-blood RNA-expression data at 7, 10, and 17 days post-dose 2 relative to pre-vaccination could be used to classify vaccine recipients into gene-signature positive or gene-signature negative groups. In conclusion, whole blood sampled from the 7, 10, 14, or 17 day post-vaccination time points, in addition to pre-vaccination, could be selected to assess potentially clinically relevant responses to M72/AS01 using transcriptome analysis.
Publication Title
Adjuvant-Associated Peripheral Blood mRNA Profiles and Kinetics Induced by the Adjuvanted Recombinant Protein Candidate Tuberculosis Vaccine M72/AS01 in Bacillus Calmette-Guérin-Vaccinated Adults.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Immunization with adjuvanted antigen results in coordinate changes in gene expression. Combination adjuvants exploit the interplay between different immunostimulants to promote immune response to vaccination. The Adjuvant System 01 (AS01) is a liposome-based combination adjuvant which contains two immunostimulants, MPL and QS-21 Here, we assess the contribution of the components of AS01 on its immunogenicity by comparing the transcriptional response induced in the draining lymph node by AS01, MPL and QS-21 at 2,4 or 6h after intramuscolar (i.m.) immunization
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The oil-in-water emulsion Adjuvant System 03 (AS03) is one of the few adjuvants used in licensed vaccines. AS03 induces a local and transient inflammatory response that contribute to its adjuvant effect. This data provides a more comprehensive analysis of early gene expression both at the injection site and in the draining lymph node 2, 4 or 6 hours after immunisation with AS03.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The goal of this study was to identify the transcriptional mechanisms involved in the activation of the immune system by QS-21, a triterpene glycoside purified from the bark of Quillaja saponaria which has adjuvant activity in vivo. Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the Malaria and Zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169+ resident macrophages of the draining lymph node where it elicited a local innate immune response. Depletion of these cells abrogated QS-21-mediated innate cell recruitment to the lymph node, dendritic cell (DC) phenotypic maturation as well as the adjuvant effect on T cell and antibody responses to co-administered antigens. DCs rather than lymph node-resident macrophages were directly involved in T cell priming by QS-21 as revealed by the decrease in antigen-specific T cell response in Batf3/ mice. Further analysis showed that the adjuvant effect of QS-21 depended on the integration of Caspase-1 and MyD88 pathways, at least in part through the local release of HMGB1. Taken together, this work unravels the key role of lymph node sentinel macrophage in controlling the adjuvant effect of a molecule proven to improve vaccine response in humans
Publication Title
Central Role of CD169<sup>+</sup> Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To study the effects of treatment with an inhaled PI3Kδ inhibitor during recovery from an exacerbation of Chronic Obstructive Pulmonary Disease (COPD) due to corrective effects on neutrophils that display dysregulated migration characteristics. We aimed to develop novel induced sputum endpoints to demonstrate changes in neutrophil phenotype and proof of mechanism of action in the lung.
Publication Title
Exploring PI3Kδ Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled Trials.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 122 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
All the sorted Treg cells are gated on CD4+CD25+CD127(low), followed by gating on various subsets using markers indicated in the sample names.
Publication Title
Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rationale: The acute respiratory distress syndrome is refractory to pharmacological intervention. Inappropriate activation of alveolar neutrophils is believed to underpin this diseases complex pathophysiology, yet these cells have been little studied.
Publication Title
Acute Respiratory Distress Syndrome Neutrophils Have a Distinct Phenotype and Are Resistant to Phosphoinositide 3-Kinase Inhibition.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Time
View Samples- Homo sapiens
- 81 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Experiment conducted to reverse engineer the transriptional response network of cytokines, growth factors and small molecular inhibitors in HLF cells.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
There is a need for non-invasive imaging protocols to support early phase clinical studies for drugs targeting neutrophilic inflammation. The aim of the study was to quantify whole lung neutrophil accumulation in (i) healthy volunteers (HV) following inhaled lipopolysaccharide (LPS) or saline and (ii) stable COPD patients, using radiolabelled autologous neutrophils and single-photon-emission/computed-tomography (SPECT/CT).
Publication Title
No associated publication
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples