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Transcriptional signatures of influenza A/H1N1-specific IgG memory-like B cell response in older individuals.

ABSTRACT: Studies suggest that the recall-based humoral immune responses to influenza A/H1N1 originates from activated memory B cells. The aim of this study was to identify baseline, early and late blood transcriptional signatures (in peripheral blood mononuclear cells/PBMCs) associated with memory B cell response following influenza vaccination.We used pre- and post-vaccination mRNA-Seq transcriptional profiling on samples from 159 subjects (50-74years old) following receipt of seasonal trivalent influenza vaccine containing the A/California/7/2009/H1N1-like virus, and penalized regression modeling to identify associations with influenza A/H1N1-specific memory B cell ELISPOT response after vaccination.Genesets and genes (p-value range 7.92E(-08) to 0.00018, q-value range 0.00019-0.039) demonstrating significant associations (of gene expression levels) with memory B cell response suggest the importance of metabolic (cholesterol and lipid metabolism-related), cell migration/adhesion, MAP kinase, NF-kB cell signaling (chemokine/cytokine signaling) and transcriptional regulation gene signatures in the development of memory B cell response after influenza vaccination.Through an unbiased transcriptome-wide profiling approach, our study identified signatures of memory B cell response following influenza vaccination, highlighting the underappreciated role of metabolic changes (among the other immune function-related events) in the regulation of influenza vaccine-induced immune memory.

SUBMITTER: Haralambieva IH

PROVIDER: S-EPMC5520794 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Transcriptional signatures of influenza A/H1N1-specific IgG memory-like B cell response in older individuals.

Haralambieva Iana H IH Ovsyannikova Inna G IG Kennedy Richard B RB Zimmermann Michael T MT Grill Diane E DE Oberg Ann L AL Poland Gregory A GA

Vaccine 20160620 34

<h4>Background</h4>Studies suggest that the recall-based humoral immune responses to influenza A/H1N1 originates from activated memory B cells. The aim of this study was to identify baseline, early and late blood transcriptional signatures (in peripheral blood mononuclear cells/PBMCs) associated with memory B cell response following influenza vaccination.<h4>Methods</h4>We used pre- and post-vaccination mRNA-Seq transcriptional profiling on samples from 159 subjects (50-74years old) following re ...[more]

PMID: 27317456

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Project description:Although influenza causes significant morbidity and mortality in the elderly, the factors underlying the reduced vaccine immunogenicity and efficacy in this age group are not completely understood. Age and immunosenescence factors, and their impact on humoral immunity after influenza vaccination, are of growing interest for the development of better vaccines for the elderly.We assessed associations between age and immunosenescence markers (T cell receptor rearrangement excision circles - TREC content, peripheral white blood cell telomerase - TERT expression and CD28 expression on T cells) and influenza A/H1N1 vaccine-induced measures of humoral immunity in 106 older subjects at baseline and three timepoints post-vaccination.TERT activity (TERT mRNA expression) was significantly positively correlated with the observed increase in the influenza-specific memory B cell ELISPOT response at Day 28 compared to baseline (p-value=0.025). TREC levels were positively correlated with the baseline and early (Day 3) influenza A/H1N1-specific memory B cell ELISPOT response (p-value=0.042 and p-value=0.035, respectively). The expression and/or expression change of CD28 on CD4+ and/or CD8+ T cells at baseline and Day 3 was positively correlated with the influenza A/H1N1-specific memory B cell ELISPOT response at baseline, Day 28 and Day 75 post-vaccination. In a multivariable analysis, the peak antibody response (HAI and/or VNA at Day 28) was negatively associated with age, the percentage of CD8+CD28 low T cells, IgD+CD27- naïve B cells, and percentage overall CD20- B cells and plasmablasts, measured at Day 3 post-vaccination. The early change in influenza-specific memory B cell ELISPOT response was positively correlated with the observed increase in influenza A/H1N1-specific HAI antibodies at Day 28 and Day 75 relative to baseline (p-value=0.007 and p-value=0.005, respectively).Our data suggest that influenza-specific humoral immunity is significantly influenced by age, and that specific markers of immunosenescence (e.g., the baseline/early expression of CD28 on CD4+ and/or CD8+ T cells and T cell immune abnormalities) are correlated with different humoral immune response outcomes observed after vaccination in older individuals, and thus can be potentially used to predict vaccine immunogenicity.

Dataset Information

Transcriptional signatures of influenza A/H1N1-specific IgG memory-like B cell response in older individuals.

Publications

Transcriptional signatures of influenza A/H1N1-specific IgG memory-like B cell response in older individuals.

Similar Datasets

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