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Systems Biology pp 117–142Cite as

Systems Biology of Vaccination in the Elderly

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 363))

Abstract

Aging population demographics, combined with suboptimal vaccine responses in the elderly, make the improvement of vaccination strategies in the elderly a developing public health issue. The immune system changes with age, with innate and adaptive cell components becoming increasingly dysfunctional. As such, vaccine responses in the elderly are impaired in ways that differ depending on the type of vaccine (e.g., live attenuated, polysaccharide, conjugate, or subunit) and the mediators of protection (e.g., antibody and/or T cell). The rapidly progressing field of systems biology has been shown to be useful in predicting immunogenicity and offering insights into potential mechanisms of protection in young adults. Future application of systems biology to vaccination in the elderly may help to identify gene signatures that predict suboptimal responses and help to identify more accurate correlates of protection. Moreover, the identification of specific defects may be used to target novel vaccination strategies that improve efficacy in elderly populations.

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References

  • Adachi K, Davis M (2011) T-cell receptor ligation induces distinct signaling pathways in naive vs. antigen-experienced T cells. Procl Natl Acad Sci USA 108:1549–1603

    Article  CAS  Google Scholar 

  • Ademokun A, Wu Y-C, Dunn-Walters D (2010) The ageing B cell population: composition and function. Biogerontology 11:125–162

    Article  PubMed  Google Scholar 

  • Agius E, Lacy K, Vukmanovic-Stejic M, Jagger A, Papageorgiou A-P, Hall S, Reed J, Curnow S, Fuentes-Duculan J, Buckley C, Salmon M, Taams L, Krueger J, Greenwood J, Klein N, Rustin M, Akbar A (2009) Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4 + T cells during aging. J Exp Med 206:1929–1969

    Article  PubMed  CAS  Google Scholar 

  • Agrawal A, Agrawal S, Cao J-N, Su H, Osann K, Gupta S (2007) Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol 178:6912–6934

    PubMed  CAS  Google Scholar 

  • Arvin A (2005) Aging, immunity, and the varicella-zoster virus. N Engl J Med 352:2266–2273

    Article  PubMed  CAS  Google Scholar 

  • Avci FY, Li X, Tsuji M, Kasper DL (2011) A mechanism for glycoconjugate vaccine activation of the adaptive immune system and its implications for vaccine design. Nat Med 17:1602–1609

    Article  PubMed  CAS  Google Scholar 

  • Barwick R (2004) History of thymoma and yellow fever vaccination. Lancet 364:936

    Article  Google Scholar 

  • Bendall SC, Simonds EF, Qiu P, Amir el AD, Krutzik PO, Finck R, Bruggner RV, Melamed R, Trejo A, Ornatsky OI, Balderas RS, Plevritis SK, Sachs K, Pe’er D, Tanner SD, Nolan GP (2011) Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332:687–696

    Article  PubMed  CAS  Google Scholar 

  • Cavanagh MM, Qi Q, Weyand CM, Goronzy JJ (2011) Finding balance: T cell regulatory receptor expression during aging. Aging Dis 2:398–413

    PubMed  Google Scholar 

  • CDC (2010a) Estimates of deaths associated with seasonal influenza—United States, 1976–2007. MMWR Morb Mortal Wkly Rep 59:1057–1062

    Google Scholar 

  • CDC (2010b) Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). MMWR Morb Mortal Wkly Rep 59:1102–1106

    Google Scholar 

  • Chapman R, Cross K, Fleming D (2003) The incidence of shingles and its implications for vaccination policy. Vaccine 21:2541–2548

    Article  PubMed  Google Scholar 

  • Chen W, Cross A, Edelman R, Sztein M, Blackwelder W, Pasetti M (2011) Antibody and Th1-type cell-mediated immune responses in elderly and young adults immunized with the standard or a high dose influenza vaccine. Vaccine 29:2865–2938

    Article  PubMed  CAS  Google Scholar 

  • Clutterbuck EA, Lazarus R, Yu LM, Bowman J, Bateman EA, Diggle L, Angus B, Peto TE, Beverley PC, Mant D, Pollard AJ (2012) Pneumococcal conjugate and plain polysaccharide vaccines have divergent effects on antigen-specific B cells. J Infect Dis 205:1408–1416

    Article  PubMed  CAS  Google Scholar 

  • Couch RB, Winokur P, Brady R, Belshe R, Chen WH, Cate TR, Sigurdardottir B, Hoeper A, Graham IL, Edelman R, He F, Nino D, Capellan J, Ruben FL (2007) Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects. Vaccine 25:7656–7663

    Article  PubMed  CAS  Google Scholar 

  • Czesnikiewicz-Guzik M, Lee W-W, Cui D, Hiruma Y, Lamar D, Yang Z-Z, Ouslander J, Weyand C, Goronzy J (2008) T cell subset-specific susceptibility to aging. Clin Immunol 127:107–125

    Article  PubMed  CAS  Google Scholar 

  • de Roux A, Schmole-Thoma B, Siber GR, Hackell JG, Kuhnke A, Ahlers N, Baker SA, Razmpour A, Emini EA, Fernsten PD, Gruber WC, Lockhart S, Burkhardt O, Welte T, Lode HM (2008) Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory. Clin Infect Dis 46:1015–1023

    Article  PubMed  Google Scholar 

  • Della Bella S, Bierti L, Presicce P, Arienti R, Valenti M, Saresella M, Vergani C, Villa M (2007) Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin Immunol 122:220–228

    Article  PubMed  CAS  Google Scholar 

  • den Braber I, Mugwagwa T, Vrisekoop N, Westera L, Mögling R, de Boer A, Willems N, Schrijver E, Spierenburg G, Gaiser K, Mul E, Otto S, Ruiter A, Ackermans M, Miedema F, Borghans J, de Boer R, Tesselaar K (2012) Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity 36:288–385

    Article  CAS  Google Scholar 

  • Faenzi E, Zedda L, Bardelli M, Spensieri F, Borgogni E, Volpini G, Buricchi F, Pasini F, Capecchi P, Montanaro F, Belli R, Lattanzi M, Piccirella S, Montomoli E, Ahmed S, Rappuoli R, Del Giudice G, Finco O, Castellino F, Galli G (2012) One dose of an MF59-adjuvanted pandemic A/H1N1 vaccine recruits pre-existing immune memory and induces the rapid rise of neutralizing antibodies. Vaccine 30:4086–4094

    Article  PubMed  CAS  Google Scholar 

  • Feng J, Gulati U, Zhang X, Keitel W, Thompson D, James J, Thompson L, Air G (2009) Antibody quantity versus quality after influenza vaccination. Vaccine 27:6358–6420

    Article  PubMed  CAS  Google Scholar 

  • Finlay D, Cantrell D (2011) Metabolism, migration and memory in cytotoxic T cells. Nat Rev Immunol 11:109–126

    Article  PubMed  CAS  Google Scholar 

  • Frasca D, Diaz A, Romero M, Landin AM, Phillips M, Lechner SC, Ryan JG, Blomberg BB (2010) Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans. Vaccine 28:8077–8084

    Article  PubMed  CAS  Google Scholar 

  • Frasca D, Diaz A, Romero M, Phillips M, Mendez NV, Landin AM, Blomberg BB (2012) Unique biomarkers for B-cell function predict the serum response to pandemic H1N1 influenza vaccine. Int Immunol 24:175–182

    Article  PubMed  CAS  Google Scholar 

  • Frasca D, Landin A, Lechner S, Ryan J, Schwartz R, Riley R, Blomberg B (2008) Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells. J Immunol 180:5283–5373

    PubMed  CAS  Google Scholar 

  • Fulop T, Larbi A, Douziech N, Levesque I, Varin A, Herbein G (2006) Cytokine receptor signalling and aging. Mech Ageing Dev 127:526–563

    Article  PubMed  CAS  Google Scholar 

  • Gaucher D, Therrien R, Kettaf N, Angermann BR, Boucher G, Filali-Mouhim A, Moser JM, Mehta RS, Drake DR, 3rd, Castro E, Akondy R, Rinfret A, Yassine-Diab B, Said EA, Chouikh Y, Cameron MJ, Clum R, Kelvin D, Somogyi R, Greller LD, Balderas RS, Wilkinson P, Pantaleo G, Tartaglia J, Haddad EK, Sekaly RP (2008) Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses. J Exp Med 205:3119–3131

    Article  PubMed  CAS  Google Scholar 

  • Gibson K, Wu Y-C, Barnett Y, Duggan O, Vaughan R, Kondeatis E, Nilsson B-O, Wikby A, Kipling D, Dunn-Walters D (2009) B-cell diversity decreases in old age and is correlated with poor health status. Aging cell 8:18–43

    Article  PubMed  CAS  Google Scholar 

  • Goodwin K, Viboud C, Simonsen L (2006) Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine 24:1159–1169

    Article  PubMed  CAS  Google Scholar 

  • Goronzy JJ, Li G, Yu M, Weyand CM (2012) Signaling pathways in aged T cells—a reflection of T cell differentiation, cell senescence and host environment. Semin Immunol (in press)

    Google Scholar 

  • Guckian JC, Christensen GD, Fine DP (1980) The role of opsonins in recovery from experimental pneumococcal pneumonia. J Infect Dis 142:175–190

    Article  PubMed  CAS  Google Scholar 

  • Hill DR (2000) Health problems in a large cohort of Americans traveling to developing countries. J Travel Med 7:259–266

    Article  PubMed  CAS  Google Scholar 

  • Hirota Y, Kaji M, Ide S, Kajiwara J, Kataoka K, Goto S, Oka T (1997) Antibody efficacy as a keen index to evaluate influenza vaccine effectiveness. Vaccine 15:962–967

    Article  PubMed  CAS  Google Scholar 

  • Hodi F, O’Day S, McDermott D, Weber R, Sosman J, Haanen J, Gonzalez R, Robert C, Schadendorf D, Hassel J, Akerley W, van den Eertwegh A, Lutzky J, Lorigan P, Vaubel J, Linette G, Hogg D, Ottensmeier C, Lebbé C, Peschel C, Quirt I, Clark J, Wolchok J, Weber J, Tian J, Yellin M, Nichol G, Hoos A, Urba W (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–734

    Article  PubMed  CAS  Google Scholar 

  • Honda M, Mengesha E, Albano S, Nichols W, Wallace D, Metzger A, Klinenberg J, Linker-Israeli M (2001) Telomere shortening and decreased replicative potential, contrasted by continued proliferation of telomerase-positive CD8 + CD28(lo) T cells in patients with systemic lupus erythematosus. Clin Immunol 99:211–432

    Article  PubMed  CAS  Google Scholar 

  • Hutchins WA, Carlone GM, Westerink MA (1999) Elderly immune response to a TI-2 antigen: heavy and light chain use and bactericidal activity to Neisseria meningitidis serogroup C polysaccharide. J Infect Dis 179:1433–1440

    Article  PubMed  CAS  Google Scholar 

  • Ikematsu H, Nagai H, Kawashima M, Kawakami Y, Tenjinbaru K, Li P, Walravens K, Gillard P, Roman F (2012) Characterization and long-term persistence of immune response following two doses of an AS03A-adjuvanted H1N1 influenza vaccine in healthy Japanese adults. Human Vacc Immunother 8:260–266

    Google Scholar 

  • Jackson LA, Neuzil KM, Nahm MH, Whitney CG, Yu O, Nelson JC, Starkovich PT, Dunstan M, Carste B, Shay DK, Baggs J, Carlone GM (2007) Immunogenicity of varying dosages of 7-valent pneumococcal polysaccharide-protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine. Vaccine 25:4029–4037

    Article  PubMed  CAS  Google Scholar 

  • Jing Y, Shaheen E, Drake R, Chen N, Gravenstein S, Deng Y (2009) Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood. Human Immunol 70:777–861

    Article  CAS  Google Scholar 

  • Jodar L, Butler J, Carlone G, Dagan R, Goldblatt D, Kayhty H, Klugman K, Plikaytis B, Siber G, Kohberger R, Chang I, Cherian T (2003) Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants. Vaccine 21:3265–3272

    Article  PubMed  CAS  Google Scholar 

  • Johnson SE, Rubin L, Romero-Steiner S, Dykes JK, Pais LB, Rizvi A, Ades E, Carlone GM (1999) Correlation of opsonophagocytosis and passive protection assays using human anticapsular antibodies in an infant mouse model of bacteremia for Streptococcus pneumoniae. J Infect Dis 180:133–140

    Article  PubMed  CAS  Google Scholar 

  • Jumaan A, Yu O, Jackson L, Bohlke K, Galil K, Seward J (2005) Incidence of herpes zoster, before and after varicella-vaccination-associated decreases in the incidence of varicella, 1992-2002. J Infect Dis 191:2002−2009

    Article  PubMed  Google Scholar 

  • Khromava AY, Eidex RB, Weld LH, Kohl KS, Bradshaw RD, Chen RT, Cetron MS (2005) Yellow fever vaccine: an updated assessment of advanced age as a risk factor for serious adverse events. Vaccine 23:3256–3263

    Article  PubMed  Google Scholar 

  • Kitano H (2002) Computational systems biology. Nature 420:206–210

    Article  PubMed  CAS  Google Scholar 

  • Kolibab K, Smithson SL, Rabquer B, Khuder S, Westerink MA (2005) Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young adults: analysis of the variable heavy chain repertoire. Infect Immun 73:7465–7476

    Article  PubMed  CAS  Google Scholar 

  • Lee W-W, Cui D, Czesnikiewicz-Guzik M, Vencio R, Shmulevich I, Aderem A, Weyand C, Goronzy J (2008) Age-dependent signature of metallothionein expression in primary CD4 T cell responses is due to sustained zinc signaling. Rejuvenation Res 11:1001–1012

    Article  PubMed  CAS  Google Scholar 

  • Lescale C, Dias S, Maës J, Cumano A, Szabo P, Charron D, Weksler M, Dosquet C, Vieira P, Goodhardt M (2010) Reduced EBF expression underlies loss of B-cell potential of hematopoietic progenitors with age. Aging cell 9:410–419

    Article  PubMed  CAS  Google Scholar 

  • Li Q-J, Chau J, Ebert P, Sylvester G, Min H, Liu G, Braich R, Manoharan M, Soutschek J, Skare P, Klein L, Davis M, Chen C-Z (2007) miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129:147–208

    Article  PubMed  CAS  Google Scholar 

  • Lindsey NP, Schroeder BA, Miller ER, Braun MM, Hinckley AF, Marano N, Slade BA, Barnett ED, Brunette GW, Horan K, Staples JE, Kozarsky PE, Hayes EB (2008) Adverse event reports following yellow fever vaccination. Vaccine 26:6077–6082

    Article  PubMed  CAS  Google Scholar 

  • Longo DM, Louie B, Putta S, Evensen E, Ptacek J, Cordeiro J, Wang E, Pos Z, Hawtin RE, Marincola FM, Cesano A (2012) Single-cell network profiling of peripheral blood mononuclear cells from healthy donors reveals age- and race-associated differences in immune signaling pathway activation. J Immunol 188:1717–1725

    Article  PubMed  CAS  Google Scholar 

  • Martin M, Weld LH, Tsai TF, Mootrey GT, Chen RT, Niu M, Cetron MS (2001) Advanced age a risk factor for illness temporally associated with yellow fever vaccination. Emerg Infect Dis 7:945–951

    Article  PubMed  CAS  Google Scholar 

  • Mazmanian SK, Kasper DL (2006) The love-hate relationship between bacterial polysaccharides and the host immune system. Nat Rev Immunol 6:849–858

    Article  PubMed  CAS  Google Scholar 

  • McElhaney JE, Xie D, Hager WD, Barry MB, Wang Y, Kleppinger A, Ewen C, Kane KP, Bleackley RC (2006) T cell responses are better correlates of vaccine protection in the elderly. J Immunol 176:6333–6339

    PubMed  CAS  Google Scholar 

  • McKenna R, Washington L, Aquino D, Picker L, Kroft S (2001) Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood 98:2498–3005

    Article  PubMed  CAS  Google Scholar 

  • McMahon BJ, Williams J, Bulkow L, Snowball M, Wainwright R, Kennedy M, Krause D (1995) Immunogenicity of an inactivated hepatitis a vaccine in Alaska Native children and Native and non-Native adults. J Infect Dis 171:676–679

    Article  PubMed  CAS  Google Scholar 

  • McMichael AJ, Gotch FM, Noble GR, Beare PA (1983) Cytotoxic T-cell immunity to influenza. N Engl J Med 309:13–17

    Article  PubMed  CAS  Google Scholar 

  • Melegaro A, Edmunds WJ (2004) The 23-valent pneumococcal polysaccharide vaccine. Part I. Efficacy of PPV in the elderly: a comparison of meta-analyses. Eur J Epidemiol 19:353–363

    Article  PubMed  CAS  Google Scholar 

  • Miller R, Jacobson B, Weil G, Simons E (1987) Diminished calcium influx in lectin-stimulated T cells from old mice. J Cell Physiol 132:337–379

    Article  PubMed  CAS  Google Scholar 

  • Monath TP, Cetron MS, McCarthy K, Nichols R, Archambault WT, Weld L, Bedford P (2005) Yellow fever 17D vaccine safety and immunogenicity in the elderly. Hum Vaccin 1:207–214

    Article  PubMed  Google Scholar 

  • Musher DM, Phan HM, Watson DA, Baughn RE (2000) Antibody to capsular polysaccharide of Streptococcus pneumoniae at the time of hospital admission for Pneumococcal pneumonia. J Infect Dis 182:158–167

    Article  PubMed  CAS  Google Scholar 

  • Nakaya HI, Li S, Pulendran B (2012) Systems vaccinology: learning to compute the behavior of vaccine induced immunity. Wiley Interdiscip Rev Syst Biol Med 4:193–205

    Article  PubMed  CAS  Google Scholar 

  • Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li GM, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R, Pulendran B (2011) Systems biology of vaccination for seasonal influenza in humans. Nat Immunol 12:786–795

    Article  PubMed  CAS  Google Scholar 

  • Naylor K, Li G, Vallejo A, Lee W-W, Koetz K, Bryl E, Witkowski J, Fulbright J, Weyand C, Goronzy J (2005) The influence of age on T cell generation and TCR diversity. J Immunol 174:7446–7498

    PubMed  CAS  Google Scholar 

  • Nikolich-Žugich J, Li G, Uhrlaub J, Renkema K, Smithey M (2012) Age-related changes in CD8 T cell homeostasis and immunity to infection. Semin Immunol (in press)

    Google Scholar 

  • Nyugen J, Agrawal S, Gollapudi S, Gupta S (2010) Impaired functions of peripheral blood monocyte subpopulations in aged humans. J Clin Immunol 30:806–819

    Article  PubMed  CAS  Google Scholar 

  • O’Shea J, Plenge R (2012) JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated Disease. Immunity 36:542–550

    Article  PubMed  CAS  Google Scholar 

  • Ortqvist A, Hedlund J, Burman LA, Elbel E, Hofer M, Leinonen M, Lindblad I, Sundelof B, Kalin M (1998) Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people. Swedish Pneumococcal Vaccination Study Group. Lancet 351:399–403

    Article  PubMed  CAS  Google Scholar 

  • Osterholm MT, Kelley NS, Sommer A, Belongia EA (2012) Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 12: 36–44

    Article  PubMed  Google Scholar 

  • Ouyang Q, Wagner W, Voehringer D, Wikby A, Klatt T, Walter S, Müller C, Pircher H, Pawelec G (2003) Age-associated accumulation of CMV-specific CD8 + T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1). Exp Gerontol 38:911–931

    Article  PubMed  CAS  Google Scholar 

  • Oxman M, Levin M, Johnson G, Schmader K, Straus S, Gelb L, Arbeit R, Simberkoff M, Gershon A, Davis L, Weinberg A, Boardman K, Williams H, Zhang J, Peduzzi P, Beisel C, Morrison V, Guatelli J, Brooks P, Kauffman C, Pachucki C, Neuzil K, Betts R, Wright P, Griffin M, Brunell P, Soto N, Marques A, Keay S, Goodman R, Cotton D, Gnann J, Loutit J, Holodniy M, Keitel W, Crawford G, Yeh SS, Lobo Z, Toney J, Greenberg R, Keller P, Harbecke R, Hayward A, Irwin M, Kyriakides T, Chan C, Chan I, Wang W, Annunziato P, Silber J, Shingles Prevention Study G (2005) A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 352:2271–2355

    Article  Google Scholar 

  • Palache A, Beyer W, Lüchters G, Völker R, Sprenger M, Masurel N (1993) Influenza vaccines: the effect of vaccine dose on antibody response in primed populations during the ongoing interpandemic period. A review of the literature. Vaccine 11:892–1800

    Article  PubMed  CAS  Google Scholar 

  • Panda A, Qian F, Mohanty S, van Duin D, Newman F, Zhang L, Chen S, Towle V, Belshe R, Fikrig E, Allore H, Montgomery R, Shaw A (2010) Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol 184:2518–2545

    Article  PubMed  CAS  Google Scholar 

  • Pang W, Price E, Sahoo D, Beerman I, Maloney W, Rossi D, Schrier S, Weissman I (2011) Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Procl Natl Acad Sci USA 108:20012–20019

    Article  CAS  Google Scholar 

  • Park S, Nahm MH (2011) Older adults have a low capacity to opsonize pneumococci due to low IgM antibody response to pneumococcal vaccinations. Infect Immun 79:314–320

    Article  PubMed  CAS  Google Scholar 

  • Pearce E, Walsh M, Cejas P, Harms G, Shen H, Wang L-S, Jones R, Choi Y (2009) Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 460:103–110

    Article  PubMed  CAS  Google Scholar 

  • Pulendran B (2009) Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology. Nat Rev Immunol 9:741–747

    PubMed  CAS  Google Scholar 

  • Pulendran B, Li S, Nakaya HI (2010) Systems vaccinology. Immunity 33:516–529

    Article  PubMed  CAS  Google Scholar 

  • Pulendran B, Miller J, Querec TD, Akondy R, Moseley N, Laur O, Glidewell J, Monson N, Zhu T, Zhu H, Staprans S, Lee D, Brinton MA, Perelygin AA, Vellozzi C, Brachman P, Jr., Lalor S, Teuwen D, Eidex RB, Cetron M, Priddy F, del Rio C, Altman J, Ahmed R (2008) Case of yellow fever vaccine–associated viscerotropic disease with prolonged viremia, robust adaptive immune responses, and polymorphisms in CCR5 and RANTES genes. J Infect Dis 198:500–507

    Article  PubMed  Google Scholar 

  • Querec T, Akondy R, Lee E, Cao W, Nakaya H, Teuwen D, Pirani A, Gernert K, Deng J, Marzolf B, Kennedy K, Wu H, Bennouna S, Oluoch H, Miller J, Vencio R, Mulligan M, Aderem A, Ahmed R, Pulendran B (2008) Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol 10:116–141

    Article  PubMed  CAS  Google Scholar 

  • Querec T, Bennouna S, Alkan S, Laouar Y, Gorden K, Flavell R, Akira S, Ahmed R, Pulendran B (2006) Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J Exp Med 203:413–437

    Article  PubMed  Google Scholar 

  • Reuman PD, Kubilis P, Hurni W, Brown L, Nalin D (1997) The effect of age and weight on the response to formalin inactivated, alum-adjuvanted hepatitis A vaccine in healthy adults. Vaccine 15:1157–1161

    Article  PubMed  CAS  Google Scholar 

  • Rogers P, Croft M (1999) Peptide dose, affinity, and time of differentiation can contribute to the Th1/Th2 cytokine balance. J Immunol 163:1205–1218

    PubMed  CAS  Google Scholar 

  • Romero-Steiner S, Musher DM, Cetron MS, Pais LB, Groover JE, Fiore AE, Plikaytis BD, Carlone GM (1999) Reduction in functional antibody activity against Streptococcus pneumoniae in vaccinated elderly individuals highly correlates with decreased IgG antibody avidity. Clin Infect Dis 29:281–288

    Article  PubMed  CAS  Google Scholar 

  • Rossi M, Yokota T, Medina K, Garrett K, Comp P, Schipul A, Kincade P (2003) B lymphopoiesis is active throughout human life, but there are developmental age-related changes. Blood 101:576–660

    Article  PubMed  CAS  Google Scholar 

  • Roukens AH, Soonawala D, Joosten SA, de Visser AW, Jiang X, Dirksen K, de Gruijter M, van Dissel JT, Bredenbeek PJ, Visser LG (2011) Elderly subjects have a delayed antibody response and prolonged viraemia following yellow fever vaccination: a prospective controlled cohort study. PLoS One 6:e27753

    Article  PubMed  CAS  Google Scholar 

  • Rubins JB, Puri AK, Loch J, Charboneau D, MacDonald R, Opstad N, Janoff EN (1998) Magnitude, duration, quality, and function of pneumococcal vaccine responses in elderly adults. J Infect Dis 178:431–440

    Article  PubMed  CAS  Google Scholar 

  • Rudd B, Venturi V, Li G, Samadder P, Ertelt J, Way S, Davenport M, Nikolich-Žugich J (2011) Nonrandom attrition of the naive CD8 + T-cell pool with aging governed by T-cell receptor:pMHC interactions. Procl Natl Acad Sci USA 108:13694–13703

    Article  CAS  Google Scholar 

  • Sablan B, Kim D, Barzaga N, Chow W, Cho M, Ahn S, Hwang S, Lee J, Namini H, Heyward W (2012) Demonstration of safety and enhanced seroprotection against hepatitis B with investigational HBsAg-1018 ISS vaccine compared to a licensed hepatitis B vaccine. Vaccine 30:2689–2785

    Article  PubMed  CAS  Google Scholar 

  • Sasaki S, He XS, Holmes TH, Dekker CL, Kemble GW, Arvin AM, Greenberg HB (2008) Influence of prior influenza vaccination on antibody and B-cell responses. PLoS One 3:e2975

    Article  PubMed  CAS  Google Scholar 

  • Sasaki S, Sullivan M, Narvaez CF, Holmes TH, Furman D, Zheng NY, Nishtala M, Wrammert J, Smith K, James JA, Dekker CL, Davis MM, Wilson PC, Greenberg HB, He XS (2011) Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies. J Clin Invest 121:3109–3119

    Article  PubMed  CAS  Google Scholar 

  • Sauce D, Larsen M, Fastenackels S, Duperrier A, Keller M, Grubeck-Loebenstein B, Ferrand C, Debré P, Sidi D, Appay V (2009) Evidence of premature immune aging in patients thymectomized during early childhood. J Clin Invest 119:3070–3078

    Article  PubMed  CAS  Google Scholar 

  • Schenkein JG, Park S, Nahm MH (2008) Pneumococcal vaccination in older adults induces antibodies with low opsonic capacity and reduced antibody potency. Vaccine 26:5521–5526

    Article  PubMed  CAS  Google Scholar 

  • Shapiro ED, Berg AT, Austrian R, Schroeder D, Parcells V, Margolis A, Adair RK, Clemens JD (1991) The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 325:1453–1460

    Article  PubMed  CAS  Google Scholar 

  • Shi Y, Yamazaki T, Okubo Y, Uehara Y, Sugane K, Agematsu K (2005) Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J Immunol 175:3262–3267

    PubMed  CAS  Google Scholar 

  • Snelgrove R, Cornere M, Edwards L, Dagg B, Keeble J, Rodgers A, Lyonga D, Stewart G, Young D, Walker B, Hussell T (2012) OX40 ligand fusion protein delivered simultaneously with the BCG vaccine provides superior protection against murine Mycobacterium tuberculosis infection. J Infect Dis 205:975–1058

    Article  PubMed  CAS  Google Scholar 

  • Staples JE, Gershman M, Fischer M (2010) Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 59:1–27

    Google Scholar 

  • Stiasny K, Aberle J, Keller M, Grubeck-Loebenstein B, Heinz F (2012) Age affects quantity but not quality of antibody responses after vaccination with an inactivated flavivirus vaccine against tick-borne encephalitis. PLoS One 7:e34145

    Google Scholar 

  • Tarazona R, DelaRosa O, Alonso C, Ostos B, Espejo J, Peña J, Solana R (2000) Increased expression of NK cell markers on T lymphocytes in aging and chronic activation of the immune system reflects the accumulation of effector/senescent T cells. Mech Ageing Dev 121:77–165

    Article  PubMed  CAS  Google Scholar 

  • Theeten H, Rumke H, Hoppener FJ, Vilatimo R, Narejos S, Van Damme P, Hoet B (2007) Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines. Curr Med Res Opin 23:2729–2739

    Article  PubMed  CAS  Google Scholar 

  • Tohme RA, Awosika-Olumo D, Nielsen C, Khuwaja S, Scott J, Xing J, Drobeniuc J, Hu DJ, Turner C, Wafeeg T, Sharapov U, Spradling PR (2011) Evaluation of hepatitis B vaccine immunogenicity among older adults during an outbreak response in assisted living facilities. Vaccine 29:9316–9320

    Article  PubMed  Google Scholar 

  • Torling J, Hedlund J, Konradsen HB, Ortqvist A (2003) Revaccination with the 23-valent pneumococcal polysaccharide vaccine in middle-aged and elderly persons previously treated for pneumonia. Vaccine 22:96–103

    Article  PubMed  CAS  Google Scholar 

  • Valenzuela H, Effros R (2002) Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus. Clin Immunol 105:117–142

    Article  PubMed  CAS  Google Scholar 

  • Van Damme P, Burgess M (2004) Immunogenicity of a combined diphtheria-tetanus-acellular pertussis vaccine in adults. Vaccine 22:305–308

    Article  PubMed  CAS  Google Scholar 

  • Vaziri H, Schächter F, Uchida I, Wei L, Zhu X, Effros R, Cohen D, Harley C (1993) Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet 52:661–668

    PubMed  CAS  Google Scholar 

  • Vermeulen J, Lange J, Tyring S, Peters P, Nunez M, Poland G, Levin M, Freeman C, Chalikonda I, Li J, Smith J, Caulfield M, Stek J, Chan I, Vessey R, Schödel F, Annunziato P, Schlienger K, Silber J (2012) Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥ 60 years of age. Vaccine 30:904–914

    Article  PubMed  CAS  Google Scholar 

  • Voehringer D, Koschella M, Pircher H (2002) Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1). Blood 100:3698–4400

    Article  PubMed  CAS  Google Scholar 

  • Wagar LE, Gentleman B, Pircher H, McElhaney JE, Watts TH (2011) Influenza-specific T cells from older people are enriched in the late effector subset and their presence inversely correlates with vaccine response. PLoS One 6:e23698

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Sun Q, Morita Y, Jiang H, Gross A, Lechel A, Hildner K, Guachalla L, Gompf A, Hartmann D, Schambach A, Wuestefeld T, Dauch D, Schrezenmeier H, Hofmann W-K, Nakauchi H, Ju Z, Kestler H, Zender L, Rudolph K (2012) A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell 148:1001–1015

    Article  PubMed  CAS  Google Scholar 

  • Weinberg A, Zhang J, Oxman M, Johnson G, Hayward A, Caulfield M, Irwin M, Clair J, Smith J, Stanley H, Marchese R, Harbecke R, Williams H, Chan I, Arbeit R, Gershon A, Schödel F, Morrison V, Kauffman C, Straus S, Schmader K, Davis L, Levin M, Investigators USDoVACSPSPS (2009) Varicella-zoster virus-specific immune responses to herpes zoster in elderly participants in a trial of a clinically effective zoster vaccine. J Infect Dis 200:1068–1145

    Article  PubMed  CAS  Google Scholar 

  • West DJ, Calandra GB (1996) Vaccine induced immunologic memory for hepatitis B surface antigen: implications for policy on booster vaccination. Vaccine 14:1019–1027

    Article  PubMed  CAS  Google Scholar 

  • Weston WM, Friedland LR, Wu X, Howe B (2012) Vaccination of adults 65 years of age and older with tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Boostrix((R))): results of two randomized trials. Vaccine 30:1721–1728

    Article  PubMed  CAS  Google Scholar 

  • WHO (2002) World population ageing: 1950–2050. World assembly on ageing report, pp 11–13

    Google Scholar 

  • Wiley SR, Raman VS, Desbien A, Bailor HR, Bhardwaj R, Shakri AR, Reed SG, Chitnis CE, Carter D (2011) Targeting TLRs expands the antibody repertoire in response to a malaria vaccine. Sci Transl Med 3:93ra69

    Google Scholar 

  • Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, Lambkin-Williams R, Gilbert A, Oxford J, Nicholas B, Staples KJ, Dong T, Douek DC, McMichael AJ, Xu XN (2012) Preexisting influenza-specific CD4 + T cells correlate with disease protection against influenza challenge in humans. Nat Med 18:274–280

    Article  PubMed  CAS  Google Scholar 

  • Wolters B, Junge U, Dziuba S, Roggendorf M (2003) Immunogenicity of combined hepatitis A and B vaccine in elderly persons. Vaccine 21:3623–3628

    Article  PubMed  CAS  Google Scholar 

  • Xu J, Vallejo A, Jiang Y, Weyand C, Goronzy J (2005) Distinct transcriptional control mechanisms of killer immunoglobulin-like receptors in natural killer (NK) and in T cells. J Biol Chem 280:24277–24362

    Article  PubMed  CAS  Google Scholar 

  • Yager E, Ahmed M, Lanzer K, Randall T, Woodland D, Blackman M (2008) Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J Exp Med 205:711–734

    Article  PubMed  CAS  Google Scholar 

  • Yu M, Li G, Lee W-W, Yuan M, Cui D, Weyand C, Goronzy J (2012) Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age. Procl Natl Acad Sci USA 109:88

    Google Scholar 

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Acknowledgments

The work in the laboratory of B.P. was supported by grants U19AI090023, HHSN266200700006C, U54AI057157, R37AI48638, R37DK057665, U19AI057266, and NO1 AI50025 from the National Institutes of Health and a grant from the Bill & Melinda Gates Foundation.

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Authors and Affiliations

  1. Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA, 30329, USA

    Sai S. Duraisingham, Helder I. Nakaya & Bali Pulendran

  2. Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30329, USA

    Nadine Rouphael

  3. Department of Medicine, Stanford University, Stanford, CA, 94305, USA

    Mary M. Cavanagh & Jorg J. Goronzy

  4. Department of Medicine, Palo Alto Veteran Administration Health Care System, Palo Alto, CA, 94304, USA

    Jorg J. Goronzy

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  1. Sai S. Duraisingham
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  2. Nadine Rouphael
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  3. Mary M. Cavanagh
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  4. Helder I. Nakaya
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  5. Jorg J. Goronzy
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  6. Bali Pulendran
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Correspondence to Bali Pulendran .

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  1. , Department of Microbiology, University of Washington at Seattle, Rosen Building 258B, Seattle, 98195-7735, Washington, USA

    Michael G. Katze

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Duraisingham, S.S., Rouphael, N., Cavanagh, M.M., Nakaya, H.I., Goronzy, J.J., Pulendran, B. (2012). Systems Biology of Vaccination in the Elderly. In: Katze, M. (eds) Systems Biology. Current Topics in Microbiology and Immunology, vol 363. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2012_250

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