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

Noémie Gensous, Claudio Franceschi, Bonnie B. Blomberg, Chiara Pirazzini, Francesco Ravaioli, Davide Gentilini, Anna Maria Di Blasio, Paolo Garagnani, Daniela Frasca, Maria Giulia Bacalini

Research output: Contribution to journalArticle

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 < 50) and older (age ≥ 50) subjects and compared DNA methylation between responders and non-responders, correcting for sex and batch in each subgroup. We identified 142 differentially methylated CpG sites in the young subgroup and 305 in the old subgroup, suggesting a larger epigenetic remodeling at older ages. Interestingly, some of the differentially methylated probes mapped in genes involved in immunosenescence (CD40) and in innate immunity responses (CXCL16, ULK1, BCL11B, BTC). In conclusion, the analysis of epigenetic landscape can shed light on the biological basis of vaccine responsiveness during aging, possibly providing new appropriate biomarkers of this process.

Original languageEnglish
Pages (from-to)94-100
Number of pages7
JournalExperimental Gerontology
Volume105
DOIs
Publication statusPublished - May 1 2018

Fingerprint

DNA Methylation
Human Influenza
Blood Cells
Vaccination
Blood
Cells
Methylation
Epigenomics
Aging of materials
Genes
Biomarkers
Microarrays
Analysis of variance (ANOVA)
Hemagglutination
Assays
Vaccines
Innate Immunity
Analysis of Variance
Healthy Volunteers
Genome

Keywords

  • Aging
  • DNA methylation
  • Immunosenescence
  • Influenza vaccination

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

Responders and non-responders to influenza vaccination : A DNA methylation approach on blood cells. / Gensous, Noémie; Franceschi, Claudio; Blomberg, Bonnie B.; Pirazzini, Chiara; Ravaioli, Francesco; Gentilini, Davide; Di Blasio, Anna Maria; Garagnani, Paolo; Frasca, Daniela; Bacalini, Maria Giulia.

In: Experimental Gerontology, Vol. 105, 01.05.2018, p. 94-100.

Research output: Contribution to journalArticle

Gensous, Noémie ; Franceschi, Claudio ; Blomberg, Bonnie B. ; Pirazzini, Chiara ; Ravaioli, Francesco ; Gentilini, Davide ; Di Blasio, Anna Maria ; Garagnani, Paolo ; Frasca, Daniela ; Bacalini, Maria Giulia. / Responders and non-responders to influenza vaccination : A DNA methylation approach on blood cells. In: Experimental Gerontology. 2018 ; Vol. 105. pp. 94-100.
@article{33caf5ad795e41708c2c884a8b3fa8a7,
title = "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{\circledR} 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 < 50) and older (age ≥ 50) subjects and compared DNA methylation between responders and non-responders, correcting for sex and batch in each subgroup. We identified 142 differentially methylated CpG sites in the young subgroup and 305 in the old subgroup, suggesting a larger epigenetic remodeling at older ages. Interestingly, some of the differentially methylated probes mapped in genes involved in immunosenescence (CD40) and in innate immunity responses (CXCL16, ULK1, BCL11B, BTC). In conclusion, the analysis of epigenetic landscape can shed light on the biological basis of vaccine responsiveness during aging, possibly providing new appropriate biomarkers of this process.",
keywords = "Aging, DNA methylation, Immunosenescence, Influenza vaccination",
author = "No{\'e}mie Gensous and Claudio Franceschi and Blomberg, {Bonnie B.} and Chiara Pirazzini and Francesco Ravaioli and Davide Gentilini and {Di Blasio}, {Anna Maria} and Paolo Garagnani and Daniela Frasca and Bacalini, {Maria Giulia}",
year = "2018",
month = "5",
day = "1",
doi = "10.1016/j.exger.2018.01.019",
language = "English",
volume = "105",
pages = "94--100",
journal = "Experimental Gerontology",
issn = "0531-5565",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Responders and non-responders to influenza vaccination

T2 - A DNA methylation approach on blood cells

AU - Gensous, Noémie

AU - Franceschi, Claudio

AU - Blomberg, Bonnie B.

AU - Pirazzini, Chiara

AU - Ravaioli, Francesco

AU - Gentilini, Davide

AU - Di Blasio, Anna Maria

AU - Garagnani, Paolo

AU - Frasca, Daniela

AU - Bacalini, Maria Giulia

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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 < 50) and older (age ≥ 50) subjects and compared DNA methylation between responders and non-responders, correcting for sex and batch in each subgroup. We identified 142 differentially methylated CpG sites in the young subgroup and 305 in the old subgroup, suggesting a larger epigenetic remodeling at older ages. Interestingly, some of the differentially methylated probes mapped in genes involved in immunosenescence (CD40) and in innate immunity responses (CXCL16, ULK1, BCL11B, BTC). In conclusion, the analysis of epigenetic landscape can shed light on the biological basis of vaccine responsiveness during aging, possibly providing new appropriate biomarkers of this process.

AB - 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 < 50) and older (age ≥ 50) subjects and compared DNA methylation between responders and non-responders, correcting for sex and batch in each subgroup. We identified 142 differentially methylated CpG sites in the young subgroup and 305 in the old subgroup, suggesting a larger epigenetic remodeling at older ages. Interestingly, some of the differentially methylated probes mapped in genes involved in immunosenescence (CD40) and in innate immunity responses (CXCL16, ULK1, BCL11B, BTC). In conclusion, the analysis of epigenetic landscape can shed light on the biological basis of vaccine responsiveness during aging, possibly providing new appropriate biomarkers of this process.

KW - Aging

KW - DNA methylation

KW - Immunosenescence

KW - Influenza vaccination

UR - http://www.scopus.com/inward/record.url?scp=85041594109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041594109&partnerID=8YFLogxK

U2 - 10.1016/j.exger.2018.01.019

DO - 10.1016/j.exger.2018.01.019

M3 - Article

C2 - 29360511

AN - SCOPUS:85041594109

VL - 105

SP - 94

EP - 100

JO - Experimental Gerontology

JF - Experimental Gerontology

SN - 0531-5565

ER -