Skip to main content
Top
Published in: Immunity & Ageing 1/2017

Open Access 01-12-2017 | Short report

Long-term maintenance of diphtheria-specific antibodies after booster vaccination is hampered by latent infection with Cytomegalovirus

Authors: Birgit Weinberger, Michael Keller, Beatrix Grubeck-Loebenstein

Published in: Immunity & Ageing | Issue 1/2017

Login to get access

Abstract

Many currently used vaccines are less immunogenic in the elderly compared to young adults. The impact of latent infection with Cytomegalovirus (CMV) on vaccine-induced antibody responses has been discussed controversially. We have demonstrated that recall responses to diphtheria vaccination are frequently insufficient in elderly persons and that antibody concentrations decline substantially within 5 years. In the current study we show that within a cohort of healthy elderly (n = 87; median age 71 years, range 66–92) antibody responses to a booster vaccination against diphtheria do not differ between CMV-negative and CMV-positive individuals 4 weeks after vaccination.. However, the goal of diphtheria-vaccination is long-term protection and this is achieved by circulating anti-toxin antibodies. Diphtheria-specific antibody concentrations decline faster in CMV-positive compared to CMV-negative older adults leading to an increased proportion of persons without protective antibody concentrations 5 years after booster vaccination and endangering long-term protection. This finding could be relevant for vaccination schedules.
Appendix
Available only for authorised users
Literature
2.
go back to reference Weinberger B, Herndler-Brandstetter D, Schwanninger A, Weiskopf D, Grubeck-Loebenstein B. Biology of immune responses to vaccines in elderly persons. Clin Infect Dis. 2008;46:1078–84.CrossRefPubMed Weinberger B, Herndler-Brandstetter D, Schwanninger A, Weiskopf D, Grubeck-Loebenstein B. Biology of immune responses to vaccines in elderly persons. Clin Infect Dis. 2008;46:1078–84.CrossRefPubMed
3.
go back to reference Chen WH, Kozlovsky BF, Effros RB, Grubeck-Loebenstein B, Edelman R, Sztein MB. Vaccination in the elderly: an immunological perspective. Trends Immunol. 2009;30:351–9.CrossRefPubMedPubMedCentral Chen WH, Kozlovsky BF, Effros RB, Grubeck-Loebenstein B, Edelman R, Sztein MB. Vaccination in the elderly: an immunological perspective. Trends Immunol. 2009;30:351–9.CrossRefPubMedPubMedCentral
5.
go back to reference Lazuardi L, Jenewein B, Wolf AM, Pfister G, Tzankov A, Grubeck-Loebenstein B. Age-related loss of naive T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes. Immunology. 2005;114:37–43.CrossRefPubMedPubMedCentral Lazuardi L, Jenewein B, Wolf AM, Pfister G, Tzankov A, Grubeck-Loebenstein B. Age-related loss of naive T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes. Immunology. 2005;114:37–43.CrossRefPubMedPubMedCentral
6.
go back to reference Almanzar G, Schwaiger S, Jenewein B, Keller M, Herndler-Brandstetter D, Wurzner R, et al. Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons. J Virol. 2005;79:3675–83.CrossRefPubMedPubMedCentral Almanzar G, Schwaiger S, Jenewein B, Keller M, Herndler-Brandstetter D, Wurzner R, et al. Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons. J Virol. 2005;79:3675–83.CrossRefPubMedPubMedCentral
7.
go back to reference Arnold CR, Wolf, J, Brunner, S, Herndler-Brandstetter, D, Grubeck-Loebenstein, B. Gain and loss of T cell subsets in old age-age-related reshaping of the T cell repertoire. J Clin Immunol. 2011;in print: Arnold CR, Wolf, J, Brunner, S, Herndler-Brandstetter, D, Grubeck-Loebenstein, B. Gain and loss of T cell subsets in old age-age-related reshaping of the T cell repertoire. J Clin Immunol. 2011;in print:
8.
go back to reference Khan N, Shariff N, Cobbold M, Bruton R, Ainsworth JA, Sinclair AJ, et al. Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol. 2002;169:1984–92.CrossRefPubMed Khan N, Shariff N, Cobbold M, Bruton R, Ainsworth JA, Sinclair AJ, et al. Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol. 2002;169:1984–92.CrossRefPubMed
9.
go back to reference Weinberger B, Lazuardi L, Weiskirchner I, Keller M, Neuner C, Fischer KH, et al. Healthy aging and latent infection with CMV lead to distinct changes in CD8+ and CD4+ T-cell subsets in the elderly. Hum Immunol. 2007;68:86–90.CrossRefPubMed Weinberger B, Lazuardi L, Weiskirchner I, Keller M, Neuner C, Fischer KH, et al. Healthy aging and latent infection with CMV lead to distinct changes in CD8+ and CD4+ T-cell subsets in the elderly. Hum Immunol. 2007;68:86–90.CrossRefPubMed
10.
go back to reference Olsson J, Wikby A, Johansson B, Lofgren S, Nilsson BO, Ferguson FG. Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech Ageing Dev. 2000;121:187–201.CrossRefPubMed Olsson J, Wikby A, Johansson B, Lofgren S, Nilsson BO, Ferguson FG. Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech Ageing Dev. 2000;121:187–201.CrossRefPubMed
11.
go back to reference Simanek AM, Dowd JB, Pawelec G, MelzerD DA, Aiello AE. Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States. PLoS One. 2011;6:e16103.CrossRefPubMedPubMedCentral Simanek AM, Dowd JB, Pawelec G, MelzerD DA, Aiello AE. Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States. PLoS One. 2011;6:e16103.CrossRefPubMedPubMedCentral
12.
go back to reference Roberts ET, Haan MN, Dowd JB, Aiello AE. Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol. 2010;172:363–71.CrossRefPubMedPubMedCentral Roberts ET, Haan MN, Dowd JB, Aiello AE. Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol. 2010;172:363–71.CrossRefPubMedPubMedCentral
13.
go back to reference Frasca D, Diaz A, Romero M, Landin AM, Blomberg BB. Cytomegalovirus (CMV) seropositivity decreases B cell responses to the influenza vaccine. Vaccine. 2015;33:1433–9.CrossRefPubMedPubMedCentral Frasca D, Diaz A, Romero M, Landin AM, Blomberg BB. Cytomegalovirus (CMV) seropositivity decreases B cell responses to the influenza vaccine. Vaccine. 2015;33:1433–9.CrossRefPubMedPubMedCentral
14.
go back to reference Guma M, Angulo A, Vilches C, Gomez-Lozano N, Malats N, Lopez-Botet M. Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood. 2004;104:3664–71.CrossRefPubMed Guma M, Angulo A, Vilches C, Gomez-Lozano N, Malats N, Lopez-Botet M. Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood. 2004;104:3664–71.CrossRefPubMed
15.
go back to reference Nielsen CM, White MJ, Bottomley C, Lusa C, Rodriguez-Galan A, Turner SE, et al. Impaired NK cell responses to Pertussis and H1N1 influenza vaccine antigens in human cytomegalovirus-infected individuals. J Immunol. 2015;194:4657–67.CrossRefPubMedPubMedCentral Nielsen CM, White MJ, Bottomley C, Lusa C, Rodriguez-Galan A, Turner SE, et al. Impaired NK cell responses to Pertussis and H1N1 influenza vaccine antigens in human cytomegalovirus-infected individuals. J Immunol. 2015;194:4657–67.CrossRefPubMedPubMedCentral
16.
go back to reference Trzonkowski P, Mysliwska J, Szmit E, Wieckiewicz J, Lukaszuk K, Brydak LB, et al. Association between cytomegalovirus infection, enhanced proinflammatory response and low level of anti-hemagglutinins during the anti-influenza vaccination--an impact of immunosenescence. Vaccine. 2003;21:3826–36.CrossRefPubMed Trzonkowski P, Mysliwska J, Szmit E, Wieckiewicz J, Lukaszuk K, Brydak LB, et al. Association between cytomegalovirus infection, enhanced proinflammatory response and low level of anti-hemagglutinins during the anti-influenza vaccination--an impact of immunosenescence. Vaccine. 2003;21:3826–36.CrossRefPubMed
17.
go back to reference Derhovanessian E, Theeten H, Hahnel K, Van DP, Cools N, Pawelec G. Cytomegalovirus-associated accumulation of late-differentiated CD4 T-cells correlates with poor humoral response to influenza vaccination. Vaccine. 2013;31:685–90.CrossRefPubMed Derhovanessian E, Theeten H, Hahnel K, Van DP, Cools N, Pawelec G. Cytomegalovirus-associated accumulation of late-differentiated CD4 T-cells correlates with poor humoral response to influenza vaccination. Vaccine. 2013;31:685–90.CrossRefPubMed
18.
go back to reference den Elzen WP, Vossen AC, Cools HJ, Westendorp RG, Kroes AC, Gussekloo J. Cytomegalovirus infection and responsiveness to influenza vaccination in elderly residents of long-term care facilities. Vaccine. 2011;29:4869–74.CrossRef den Elzen WP, Vossen AC, Cools HJ, Westendorp RG, Kroes AC, Gussekloo J. Cytomegalovirus infection and responsiveness to influenza vaccination in elderly residents of long-term care facilities. Vaccine. 2011;29:4869–74.CrossRef
19.
go back to reference O'Connor D, Truck J, Lazarus R, Clutterbuck EA, Voysey M, Jeffery K, et al. The effect of chronic cytomegalovirus infection on pneumococcal vaccine responses. J Infect Dis. 2014;209:1635–41.CrossRefPubMed O'Connor D, Truck J, Lazarus R, Clutterbuck EA, Voysey M, Jeffery K, et al. The effect of chronic cytomegalovirus infection on pneumococcal vaccine responses. J Infect Dis. 2014;209:1635–41.CrossRefPubMed
20.
go back to reference Kaml M, Weiskirchner I, Keller M, Luft T, Hoster E, Hasford J, et al. Booster vaccination in the elderly: their success depends on the vaccine type applied earlier in life as well as on pre-vaccination antibody titers. Vaccine. 2006;24:6808–11.CrossRefPubMed Kaml M, Weiskirchner I, Keller M, Luft T, Hoster E, Hasford J, et al. Booster vaccination in the elderly: their success depends on the vaccine type applied earlier in life as well as on pre-vaccination antibody titers. Vaccine. 2006;24:6808–11.CrossRefPubMed
21.
go back to reference Weinberger B, Schirmer M, Matteucci GR, Siebert U, Fuchs D, Grubeck-Loebenstein B. Recall responses to tetanus and diphtheria vaccination are frequently insufficient in elderly persons. PLoS One. 2013;8:e82967.CrossRefPubMedPubMedCentral Weinberger B, Schirmer M, Matteucci GR, Siebert U, Fuchs D, Grubeck-Loebenstein B. Recall responses to tetanus and diphtheria vaccination are frequently insufficient in elderly persons. PLoS One. 2013;8:e82967.CrossRefPubMedPubMedCentral
22.
go back to reference Bulati M, Caruso C, Colonna-Romano G. From lymphopoiesis to plasma cells differentiation, the age-related modifications of B cell compartment are influenced by "inflamm-ageing". Ageing Res Rev. 2017;36:125–36.CrossRefPubMed Bulati M, Caruso C, Colonna-Romano G. From lymphopoiesis to plasma cells differentiation, the age-related modifications of B cell compartment are influenced by "inflamm-ageing". Ageing Res Rev. 2017;36:125–36.CrossRefPubMed
23.
go back to reference Frasca D, Diaz A, Romero M, Blomberg BB. Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways. Exp Gerontol. 2017;87:113–20.CrossRefPubMed Frasca D, Diaz A, Romero M, Blomberg BB. Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways. Exp Gerontol. 2017;87:113–20.CrossRefPubMed
24.
go back to reference Goldeck D, Oettinger L, Janssen N, Demuth I, Steinhagen-Thiessen E, Pawelec G. Cytomegalovirus infection minimally affects the frequencies of B-cell phenotypes in peripheral blood of younger and older adults. Gerontology. 2016;62:323–9.CrossRefPubMed Goldeck D, Oettinger L, Janssen N, Demuth I, Steinhagen-Thiessen E, Pawelec G. Cytomegalovirus infection minimally affects the frequencies of B-cell phenotypes in peripheral blood of younger and older adults. Gerontology. 2016;62:323–9.CrossRefPubMed
25.
go back to reference Wang C, Liu Y, Xu LT, Jackson KJ, Roskin KM, Pham TD, et al. Effects of aging, cytomegalovirus infection, and EBV infection on human B cell repertoires. J Immunol. 2014;192:603–11.CrossRefPubMed Wang C, Liu Y, Xu LT, Jackson KJ, Roskin KM, Pham TD, et al. Effects of aging, cytomegalovirus infection, and EBV infection on human B cell repertoires. J Immunol. 2014;192:603–11.CrossRefPubMed
26.
go back to reference Pritz T, Lair J, Ban M, Keller M, Weinberger B, Krismer M, et al. Plasma cell numbers decrease in bone marrow of old patients. Eur J Immunol. 2015;45:738–46.CrossRefPubMed Pritz T, Lair J, Ban M, Keller M, Weinberger B, Krismer M, et al. Plasma cell numbers decrease in bone marrow of old patients. Eur J Immunol. 2015;45:738–46.CrossRefPubMed
27.
go back to reference Pangrazzi L, Meryk A, Naismith E, Koziel R, Lair J, Krismer M, et al. "Inflamm-aging" influences immune cell survival factors in human bone marrow. Eur J Immunol. 2016;47(3):481–92.CrossRef Pangrazzi L, Meryk A, Naismith E, Koziel R, Lair J, Krismer M, et al. "Inflamm-aging" influences immune cell survival factors in human bone marrow. Eur J Immunol. 2016;47(3):481–92.CrossRef
Metadata
Title
Long-term maintenance of diphtheria-specific antibodies after booster vaccination is hampered by latent infection with Cytomegalovirus
Authors
Birgit Weinberger
Michael Keller
Beatrix Grubeck-Loebenstein
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2017
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/s12979-017-0099-y

Other articles of this Issue 1/2017

Immunity & Ageing 1/2017 Go to the issue