title: Cellular Interferon Gamma and Granzyme B Responses to Cytomegalovirus-pp65 and Influenza N1 Are Positively Associated in Elderly.
abstract: Morbidity and mortality in the elderly are associated with viral infections, including influenza and cytomegalovirus (CMV). With increasing age, cellular immunity gains importance in protection to influenza, but latent CMV is highly prevalent and associated with immune dysfunction. An insight into the association between immunity against influenza and CMV adds to the understanding of healthy aging. Here we first aimed to measure influenza-specific cellular immunity using granzyme B (GrzB) and interferon-gamma (IFN-γ)-ELISpot. Next, influenza-specific cellular immunity was associated with humoral and cellular CMV-specific immunity in healthy 65+ elderly. Vaccine trial participants gave additional blood samples 3 weeks after receiving a H1N1 containing vaccine. CMV serology was determined and peripheral blood mononuclear cells were stimulated with influenza N1 or CMV pp65-derived peptide pools for 7 days and rechallenged to assess antigen-specific GgrzB and IFN-γ responses using ELISpot assays. Results were compared using chi-square and correlation analysis. Eighty-three individuals (60% men, 65% CMV IgG+, age range 65-78y) participated. We found significant positive associations between IFN-γ and GrzB responses to both influenza and CMV, but also between a positive CMV serostatus and an influenza N1-specific activation marker response (p = 0.013). CMV pp65 responses were detected in CMV IgG+ individuals, but remarkably also in CMV IgG- individuals (27%). In this study, following influenza vaccination, elderly with cellular immunity against CMV were more likely to have cellular immunity against influenza vaccine N1 antigen. These findings stress the need to continue exploring the possible role of CMV in immunosenescence.
authors.affiliation: 1 Faculty of Medicine and Health Sciences, Center for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp , Antwerp, Belgium .
authors.forename: Heidi
authors.initials: H
authors.lastname: Theeten
authors.affiliation: 2 Department of Public Health and Primary Care, Katholieke Universiteit Leuven , Leuven, Belgium .
authors.forename: Catharina
authors.initials: C
authors.lastname: Mathei
authors.affiliation: 1 Faculty of Medicine and Health Sciences, Center for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp , Antwerp, Belgium .
authors.forename: Kelly
authors.initials: K
authors.lastname: Peeters
authors.affiliation: 1 Faculty of Medicine and Health Sciences, Center for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp , Antwerp, Belgium .|3 Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BIOSTAT), Hasselt University , Hasselt, Belgium .
authors.forename: Benson
authors.initials: B
authors.lastname: Ogunjimi
authors.affiliation: 1 Faculty of Medicine and Health Sciences, Center for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp , Antwerp, Belgium .
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: 1 Faculty of Medicine and Health Sciences, Center for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp , Antwerp, Belgium .
authors.forename: Margareta
authors.initials: M
authors.lastname: Ieven
authors.affiliation: 1 Faculty of Medicine and Health Sciences, Center for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp , Antwerp, Belgium .
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Damme
authors.affiliation: 1 Faculty of Medicine and Health Sciences, Center for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp , Antwerp, Belgium .
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cools
mesh_terms: D000368:Aged; D000375:Aging / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000401:mortality / Q000821:virology; D005260:Female; D053804:Granzymes / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D009439:Neuraminidase / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology*; D014611:Vaccination; D014763:Viral Matrix Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007252:Influenza Vaccines; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma; C487630:NA protein, influenza A virus; D009439:Neuraminidase; C509213:GZMB protein, human; D053804:Granzymes