Differential miRNA Expression in B Cells/T Cells Associated with Inter-individual Differences in Humoral Immune Response to Measles Vaccination
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ABSTRACT:
PROVIDER: PRJNA429049 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6494690.fastq.gz | Fastqsanger.gz | |||
| SRR6494700.fastq.gz | Fastqsanger.gz | |||
| SRR6494710.fastq.gz | Fastqsanger.gz | |||
| SRR6494720.fastq.gz | Fastqsanger.gz | |||
| SRR6494730.fastq.gz | Fastqsanger.gz |
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Project description:Through Next Generation Sequencing (mRNA-Seq) of intracellular miRNAs in measles virus-stimulated B and CD4+ T cells isolated from high and low antibody responders to measles vaccination, we identified a set of B cell-specific miRNAs (e.g., miR-151a-5p, miR-223, miR-29, miR-15a-5p, miR-199a-3p, miR-103a, and miR-15a/16 cluster) associated with measles-specific antibody response after vaccination. No CD4+ T cell-specific miRNA expression differences between high and low antibody responders were found. DIANA tool was used for gene/target prediction and pathway enrichment analysis and this yielded several biological processes/pathways, including regulation of adherens junction proteins, Fc-receptor signaling pathway, phosphatidylinositol-mediated signaling pathway, growth factor signaling pathway/pathways, transcriptional regulation, apoptosis and virus-related processes, that were significantly associated with neutralizing antibody titers after measles vaccination. This study demonstrates that miRNA expression directly or indirectly influences humoral immunity to measles vaccination and suggests that B cell-specific miRNAs may potentially serve as predictive biomarkers of vaccine response.
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Project description:BackgroundMicroRNAs are important mediators of post-transcriptional regulation of gene expression through RNA degradation and translational repression, and are emerging biomarkers of immune system activation/response after vaccination.MethodsWe performed Next Generation Sequencing (mRNA-Seq) of intracellular miRNAs in measles virus-stimulated B and CD4+ T cells from high and low antibody responders to measles vaccine. Negative binomial generalized estimating equation (GEE) models were used for miRNA assessment and the DIANA tool was used for gene/target prediction and pathway enrichment analysis.ResultsWe identified a set of B cell-specific miRNAs (e.g., miR-151a-5p, miR-223, miR-29, miR-15a-5p, miR-199a-3p, miR-103a, and miR-15a/16 cluster) and biological processes/pathways, including regulation of adherens junction proteins, Fc-receptor signaling pathway, phosphatidylinositol-mediated signaling pathway, growth factor signaling pathway/pathways, transcriptional regulation, apoptosis and virus-related processes, significantly associated with neutralizing antibody titers after measles vaccination. No CD4+ T cell-specific miRNA expression differences between high and low antibody responders were found.ConclusionOur study demonstrates that miRNA expression directly or indirectly influences humoral immunity to measles vaccination and suggests that B cell-specific miRNAs may serve as useful predictive biomarkers of vaccine humoral immune response.
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Project description:Whole blood transcriptomics analysis of healthy individuals, immunized with the trivalent 2012-2013 season flu vaccine via transcutaneous, intramuscular or intradermal route. We define an early gene expression profile, detected at day 1 after immunization, that is associated with the development of either humoral or cytotoxic CD8 T cell responses. We used System Biology approach to analyse vaccine efficacy in order to find innate predictive biomarkers of the quality of adaptive responses for potential clinical use in the future. Moreover, from a methodological point of view this study increases knowledges on how vaccine route(s) can affect resulting immune responses and into mechanisms involved in the induction of humoral and cellular immunity to influenza vaccination.
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Project description:IntroductionRepeated measles outbreaks in countries with relatively high vaccine coverage are mainly due to failure to vaccinate and importation; however, cases in immunized individuals exist raising questions about suboptimal measles vaccine-induced humoral immunity and/or waning immunity in a low measles-exposure environment.Areas coveredThe plaque reduction neutralization measurement of functional measles-specific antibodies correlates with protection is the gold standard in measles serology, but it does not assess cellular-immune or other parameters that may be associated with durable and/or protective immunity after vaccination. Additional correlates of protection and long-term immunity and new determinants/signatures of vaccine responsiveness such as specific CD46 and IFI44L genetic variants associated with neutralizing antibody titers after measles vaccination are under investigation. Current and future systems biology studies, coupled with new technology/assays and analytical approaches, will lead to an increasingly sophisticated understanding of measles vaccine-induced humoral immunity and will identify 'signatures' of protective and durable immune responses.Expert opinionThis will translate into the development of highly predictive assays of measles vaccine efficacy, effectiveness, and durability for prospective identification of potential low/non-responders and susceptible individuals who require additional vaccine doses. Such new advances may drive insights into the development of new/improved vaccine formulations and delivery systems.
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