Dataset Information

Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering.

ABSTRACT: PBMC transcriptomes after influenza vaccination contain valuable information about factors affecting vaccine responses. However, distilling meaningful knowledge out of these complex datasets is often difficult and requires advanced data mining algorithms. We investigated the use of the data-driven Weighted Gene Correlation Network Analysis (WGCNA) gene clustering method to identify vaccine response-related genes in PBMC transcriptomic datasets collected from 138 healthy older adults (ages 50-74) before and after 2010-2011 seasonal trivalent influenza vaccination. WGCNA separated the 14,197 gene dataset into 15 gene clusters based on observed gene expression patterns across subjects. Eight clusters were strongly enriched for genes involved in specific immune cell types and processes, including B cells, T cells, monocytes, platelets, NK cells, cytotoxic T cells, and antiviral signaling. Examination of gene cluster membership identified signatures of cellular and humoral responses to seasonal influenza vaccination, as well as pre-existing cellular immunity. The results of this study illustrate the utility of this publically available analysis methodology and highlight genes previously associated with influenza vaccine responses (e.g., CAMK4, CD19), genes with functions not previously identified in vaccine responses (e.g., SPON2, MATK, CST7), and previously uncharacterized genes (e.g. CORO1C, C8orf83) likely related to influenza vaccine-induced immunity due to their expression patterns.

SUBMITTER: Voigt EA

PROVIDER: S-EPMC5768803 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering.

Voigt Emily A EA Grill Diane E DE Zimmermann Michael T MT Simon Whitney L WL Ovsyannikova Inna G IG Kennedy Richard B RB Poland Gregory A GA

Scientific reports 20180115 1

PBMC transcriptomes after influenza vaccination contain valuable information about factors affecting vaccine responses. However, distilling meaningful knowledge out of these complex datasets is often difficult and requires advanced data mining algorithms. We investigated the use of the data-driven Weighted Gene Correlation Network Analysis (WGCNA) gene clustering method to identify vaccine response-related genes in PBMC transcriptomic datasets collected from 138 healthy older adults (ages 50-74) ...[more]

PMID: 29335477

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Project description:In advance of a large influenza vaccine effectiveness (VE) cohort study among older adults in Thailand, we conducted a population-based, cross-sectional survey to measure vaccine coverage and identify factors associated with influenza vaccination among older Thai adults that could bias measures of vaccine effectiveness.We selected adults ?65 years using a two-stage, stratified, cluster sampling design. Functional status was assessed using the 10-point Vulnerable Elders Survey (VES); scores ?3 indicated vulnerability. Questions about attitudes towards vaccination were based on the Health Belief Model. The distance between participants' households and the nearest vaccination clinic was calculated. Vaccination status was determined using national influenza vaccination registry. Prevalence ratios (PR) and 95% confidence intervals (CIs) were calculated using log-binomial multivariable models accounting for the sampling design.We enrolled 581 participants, of whom 60% were female, median age was 72 years, 41% had at least one chronic underlying illness, 24% met the criteria for vulnerable, and 23% did not leave the house on a daily basis. Influenza vaccination rate was 34%. In multivariable models, no variable related to functional status was associated with vaccination. The strongest predictors of vaccination were distance to the nearest vaccination center (PR 3.0, 95% CI 1.7-5.1 for participants in the closest quartile compared to the furthest), and high levels of a perception of benefits of influenza vaccination (PR 2.8, 95% CI 1.4-5.6) and cues to action (PR 2.7, 95% CI 1.5-5.1).Distance to vaccination clinics should be considered in analyses of influenza VE studies in Thailand. Strategies that emphasize benefits of vaccination and encourage physicians to recommend annual influenza vaccination could improve influenza vaccine uptake among older Thai adults. Outreach to more distant and less mobile older adults may also be required to improve influenza vaccination coverage.

Project description:The goal of annual influenza vaccination is to reduce mortality and morbidity associated with this disease through the generation of protective immune responses. The objective of the current study was to examine markers of immunosenescence and identify immunosenescence-related differences in gene expression, gene regulation, cytokine secretion, and immunologic changes in an older study population receiving seasonal influenza A/H1N1 vaccination. Surprisingly, prior studies in this cohort revealed weak correlations between immunosenescence markers and humoral immune response to vaccination. In this report, we further examined the relationship of each immunosenescence marker (age, T cell receptor excision circle frequency, telomerase expression, percentage of CD28- CD4+ T cells, percentage of CD28- CD8+ T cells, and the CD4/CD8 T cell ratio) with additional markers of immune response (serum cytokine and chemokine expression) and measures of gene expression and/or regulation. Many of the immunosenescence markers indeed correlated with distinct sets of individual DNA methylation sites, miRNA expression levels, mRNA expression levels, serum cytokines, and leukocyte subsets. However, when the individual immunosenescence markers were grouped by pathways or functional terms, several shared biological functions were identified: antigen processing and presentation pathways, MAPK, mTOR, TCR, BCR, and calcium signaling pathways, as well as key cellular metabolic, proliferation and survival activities. Furthermore, the percent of CD4+ and/or CD8+ T cells lacking CD28 expression also correlated with miRNAs regulating clusters of genes known to be involved in viral infection. Integrated (DNA methylation, mRNA, miRNA, and protein levels) network biology analysis of immunosenescence-related pathways and genesets identified both known pathways (e.g., chemokine signaling, CTL, and NK cell activity), as well as a gene expression module not previously annotated with a known function. These results may improve our ability to predict immune responses to influenza and aid in new vaccine development, and highlight the need for additional studies to better define and characterize immunosenescence.

Dataset Information

Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering.

Publications

Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering.

Similar Datasets

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