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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:Older adults experience declining influenza vaccine-induced immunity and are at higher risk of influenza and its complications. For this reason, high dose (e.g., Fluzone) and adjuvanted (e.g., Fluad) vaccines are preferentially recommended for people age 65 years and older. However, T cell transcriptional activity shaping the humoral immune responses to Fluzone and Fluad vaccines in older adults is still poorly understood. We designed a study of 234 older adults (≥65 years old) who were randomly allocated to receive Fluzone or Fluad vaccine and provided blood samples at baseline and at Day 28 after immunization. We measured the humoral immune responses (hemagglutination inhibition/HAI antibody titer) to influenza A/H3N2 and performed mRNA-Seq transcriptional profiling in purified CD4+ T cells, in order to identify T cell signatures that might explain differences in humoral immune response by vaccine type. Given the large differences in formulation (higher antigen dose vs adjuvant), our hypothesis was that each vaccine elicited a distinct transcriptomic response after vaccination. Thus, the main focus of our study was to identify the differential gene expression influencing the antibody titer in the two vaccine groups. Our analyses identified three differentially expressed, functionally linked genes/proteins in CD4+ T cells: the calcium/calmodulin dependent serine/threonine kinase IV (CaMKIV); its regulator the TMEM38B/transmembrane protein 38B, involved in maintenance of intracellular Ca2+ release; and the transcriptional coactivator CBP/CREB binding protein, as regulators of transcriptional activity/function in CD4+ T cells that impact differences in immune response by vaccine type. Significantly enriched T cell-specific pathways/biological processes were also identified that point to the importance of genes/proteins involved in Th1/Th2 cell differentiation, IL-17 signaling, calcium signaling, Notch signaling, MAPK signaling, and regulation of TRP cation Ca2+ channels in humoral immunity after influenza vaccination. In summary, we identified the genes/proteins and pathways essential for cell activation and function in CD4+ T cells that are associated with differences in influenza vaccine-induced humoral immunity by vaccine type. These findings provide an additional mechanistic perspective for achieving protective immunity in older adults.

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.

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