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

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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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Expression data from draining lymph node of mice immunized with AS01 or its components

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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

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