Human Gene Set: FISCHER_BLOOD_PLASMA_RVSV_EBOV_AGE_18_55YO_HIGH_DOSE_3DY_DN


Standard name FISCHER_BLOOD_PLASMA_RVSV_EBOV_AGE_18_55YO_HIGH_DOSE_3DY_DN
Systematic name M41072
Brief description Genes down-regulated in blood plasma 3d vs 0d in adults (18-55) (high dose) after exposure to rVSV-EBOV , time point 3D
Full description or abstract VSV-EBOV is a replication-competent Ebola virus (EBOV) vaccine, which was tested in clinical trials as response to the Ebola virus disease (EVD) outbreak 2013-2016. It is the most advanced EBOV candidate currently in the licensure process. The experimental vaccine was again administered as response to outbreaks in the Democratic Republic of Congo. However, underlying molecular mechanisms that convey protection remain incompletely understood. MicroRNAs (miRNAs) are known key regulators that influence gene expression on a post-transcriptional level. The miRNA-mediated control has emerged as a critical regulatory principle in the immune system, which strongly influences the balance of innate and adaptive immune responses by modulation of signaling pathways critical for differentiation of immune cells. We investigated expression levels of circulating miRNAs (c-miRNAs) in plasma from healthy vaccinees, as they may reflect cellular dynamics following VSV-EBOV immunization and additionally may serve as potential biomarkers for vaccine efficacy. As part of the WHO-led VEBCON consortium, we investigated safety and immunogenicity of VSV-EBOV in a phase I trial. A comprehensive analysis of expression levels on c-miRNAs from plasma samples following VSV-EBOV immunization (day 0, 1, 3 post vaccination) was conducted using RT-qPCR assays. Potential biological relevance was assessed using in silico analyses. Additionally, we correlated dynamics of miRNA expressions with our previously reported data on vaccine-induced antibody and cytokine responses and finally evaluated the prognostic power by generating ROC curves. We identified four promising miRNAs (hsa-miR-146a, hsa-miR-126, hsa-miR-199a, hsa-miR-484), showing a strong association with adaptive immune responses, exhibited favourable prognostic performance and are implicated in immunology-related functions. Our results provide evidence that miRNAs may serve as useful biomarkers for prediction of vaccine-induced immunogenicity. Furthermore, our unique data set provides insight into molecular mechanisms that underlie VSV-EBOV-mediated protective immune responses, which may help to decipher VSV-EBOV immune signature and accelerate strategic vaccine design or personalized approaches.
Collection C7: Immunologic Signature
      VAX: HIPC Vaccine Response
Source publication Pubmed 30244872   Authors: Fischer T,Spohn M,Olearo F,Zinser ME,Kasonta R,Stubbe HC,Rechtien A,Ly ML,Schmiedel S,Lohse AW,Grundhoff A,VEBCON (VSV-Ebola Consortium),Addo MM,Dahlke C
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Source species Homo sapiens
Contributed by HIPC SIGNATURES (NIAID/HIPC SIGNATURES)
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