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Transcriptional signatures to AS01-adjuvanted tuberculosis vaccine in naïve and primed participants

ABSTRACT: In this exploratory post-hoc analysis of clinical trial samples (clinicalTrials.gov: NCT01424501), we compared gene expression patterns elicited by two immunizations with the candidate tuberculosis (TB) vaccine M72/AS01, between three groups of individuals with different levels of memory responses to TB antigens before vaccination

ORGANISM(S): Homo sapiens

PROVIDER: GSE197408 | GEO | 2022/11/16

REPOSITORIES: GEO

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Systems analysis of protective immune responses to RTS,S malaria vaccination in humans

Project description:We applied a systems biology approach to study immune responses in subjects receiving 3 consecutive immunizations with RTS,S/AS01 (RRR), or in those receiving 2 immunizations of RTS,S/AS01, following a primary immunization with adenoviral Ad35 (ARR) vector expressing circumsporozoite protein.

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Project description: Not available

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Adjuvant associated peripheral-blood mRNA profiles and kinetics induced by the adjuvanted recombinant-protein candidate tuberculosis vaccine M72/AS01 in BCG-vaccinated adults

Project 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-Guérin (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.

2018-03-19 | GSE102459 | GEO

Microarray analysis of the Lysosome-dependent activation of human dendritic cells by the vaccine adjuvant QS-21.

Project description:QS-21 is a component of the Adjuvant System AS01 that is used in several vaccine candidates. QS-21 strongly potentiates both cellular and humoral immune responses to purified antigens, yet how it activates immune cells is largely unknown. Here, QS-21 (or DQ) directly activated human monocyte-derived dendritic cells (moDCs) and promoted a pro-inflammatory transcriptional program.

2017-01-30 | E-MTAB-5388 | biostudies-arrayexpress

Adjuvanted influenza vaccine dynamics.

Project description: Not available

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Project description: Not available

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A Phase 2 Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma

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A baseline transcriptional signature associates with clinical malaria risk in RTS,S/AS01-vaccinated African children

Project description:In a phase 3 trial in African infants/children, the RTS,S/AS01 (GSK) vaccine showed moderate efficacy against clinical malaria. We aimed to identify RTS,S/AS01-induced signatures associated with clinical malaria by analyzing antigen-stimulated peripheral blood mononuclear cells sampled from a subset of trial participants at baseline and month 3 (one month post-final dose). RTS,S/AS01 vaccination was associated with downregulation of B-cell and monocyte-related blood transcriptional modules (BTMs) and upregulation of T-cell related BTMs, as well as higher month 3 (vs baseline) (CSP)-specific CD4+ T-cell responses. For some RTS,S/AS01-associated BTMs, month 3 levels correlated with anti-circumsporozoite protein (CSP) IgM and inversely with anti-CSP IgG responses. There were few RTS,S/AS01-associated BTMs whose month 3 levels correlated with malaria risk. In contrast, baseline levels of dendritic cell and monocyte RTS,S/AS01-associated BTMs correlated with malaria risk. A cross-study analysis supported generalizability of these correlations to healthy, malaria-naïve adults, suggesting inflammatory monocytes may inhibit protective RTS,S/AS01-induced responses.

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