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Responders and non-responders to influenza vaccination: A DNA methylation approach on blood cells.

ABSTRACT: Several evidences indicate that aging negatively affects the effectiveness of influenza vaccination. Although it is well established that immunosenescence has an important role in vaccination response, the molecular pathways underlying this process are largely unknown. Given the importance of epigenetic remodeling in aging, here we analyzed the relationship between responsiveness to influenza vaccination and DNA methylation profiles in healthy subjects of different ages. Peripheral blood mononuclear cells were collected from 44 subjects (age range: 19-90?years old) immediately before influenza vaccination. Subjects were subsequently classified as responders or non-responders according to hemagglutination inhibition assay 4-6?weeks after the vaccination. Baseline whole genome DNA methylation in peripheral blood mononuclear cells was analyzed using the Illumina® Infinium 450?k microarray. Differential methylation analysis between the two groups (responders and non-responders) was performed through an analysis of variance, correcting for age, sex and batch. We identified 83 CpG sites having a nominal p-value <.001 and absolute difference in DNA methylation of at least 0.05 between the two groups. For some CpG sites, we observed age-dependent decrease or increase in methylation, which in some cases was specific for the responders and non-responders groups. Finally, we divided the cohort in two subgroups including younger (age?

SUBMITTER: Gensous N

PROVIDER: S-EPMC5989724 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Responders and non-responders to influenza vaccination: A DNA methylation approach on blood cells.

Gensous Noémie N Franceschi Claudio C Blomberg Bonnie B BB Pirazzini Chiara C Ravaioli Francesco F Gentilini Davide D Di Blasio Anna Maria AM Garagnani Paolo P Frasca Daniela D Bacalini Maria Giulia MG

Experimental gerontology 20180131

Several evidences indicate that aging negatively affects the effectiveness of influenza vaccination. Although it is well established that immunosenescence has an important role in vaccination response, the molecular pathways underlying this process are largely unknown. Given the importance of epigenetic remodeling in aging, here we analyzed the relationship between responsiveness to influenza vaccination and DNA methylation profiles in healthy subjects of different ages. Peripheral blood mononuc ...[more]

PMID: 29360511

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Project description:Failure to achieve a protected state after influenza vaccination is poorly understood but occurs commonly among aged populations experiencing greater immunosenescence. In order to better understand immune response in the elderly, we studied epigenetic and transcriptomic profiles and humoral immune response outcomes in 50-74 year old healthy participants. Associations between DNA methylation and gene expression reveal a system-wide regulation of immune-relevant functions, likely playing a role in regulating a participant's propensity to respond to vaccination. Our findings show that sites of methylation regulation associated with humoral response to vaccination impact known cellular differentiation signaling and antigen presentation pathways. We performed our analysis using per-site and regionally average methylation levels, in addition to continuous or dichotomized outcome measures. The genes and molecular functions implicated by each analysis were compared, highlighting different aspects of the biologic mechanisms of immune response affected by differential methylation. Both cis-acting (within the gene or promoter) and trans-acting (enhancers and transcription factor binding sites) sites show significant associations with measures of humoral immunity. Specifically, we identified a group of CpGs that, when coordinately hypo-methylated, are associated with lower humoral immune response, and methylated with higher response. Additionally, CpGs that individually predict humoral immune responses are enriched for polycomb-group and FOXP2 transcription factor binding sites. The most robust associations implicate differential methylation affecting gene expression levels of genes with known roles in immunity (e.g. HLA-B and HLA-DQB2) and immunosenescence. We believe our data and analysis strategy highlight new and interesting epigenetic trends affecting humoral response to vaccination against influenza; one of the most common and impactful viral pathogens.

Project description:Individual variability in responses to vaccination can result in vaccinated subjects failing to develop a protective immune response. Vaccine non-responders can remain susceptible to infection and may compromise efforts to achieve herd immunity. Biomarkers of vaccine unresponsiveness could aid vaccine research and development as well as strategically improve vaccine administration programs. We previously vaccinated piglets (n = 117) against a commercial Mycoplasma hyopneumoniae vaccine (RespiSure-One) and observed in low vaccine responder piglets, as defined by serum IgG antibody titers, differential phosphorylation of peptides involved in pro-inflammatory cytokine signaling within peripheral blood mononuclear cells (PBMCs) prior to vaccination, elevated plasma interferon-gamma concentrations, and lower birth weight compared to high vaccine responder piglets. In the current study, we use kinome analysis to investigate signaling events within PBMCs collected from the same high and low vaccine responders at 2 and 6 days post-vaccination. Furthermore, we evaluate the use of inflammatory plasma cytokines, birthweight, and signaling events as biomarkers of vaccine unresponsiveness in a validation cohort of high and low vaccine responders. Differential phosphorylation events (FDR < 0.05) within PBMCs are established between high and low responders at the time of vaccination and at six days post-vaccination. A subset of these phosphorylation events were determined to be consistently differentially phosphorylated (p < 0.05) in the validation cohort of high and low vaccine responders. In contrast, there were no differences in birth weight (p > 0.5) and plasma IFNγ concentrations at the time of vaccination (p > 0.6) between high and low responders within the validation cohort. The results in this study suggest, at least within this study population, phosphorylation biomarkers are more robust predictors of vaccine responsiveness than other physiological markers.

Dataset Information

Responders and non-responders to influenza vaccination: A DNA methylation approach on blood cells.

Publications

Responders and non-responders to influenza vaccination: A DNA methylation approach on blood cells.

Similar Datasets

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