Skip to main content
SpringerLink
Log in

Immune Signatures and Systems Biology of Vaccines

  • Chapter
  • First Online:
Immunologic Signatures of Rejection

Abstract

Vaccines represent a strategic successful tool to prevent or contain diseases with high morbidity or mortality. However, despite the extensive and wide use, we still have a limited knowledge on mechanisms underlying the effective elicitation of protective immune responses by vaccines, which represents the final outcome of a effective cooperation between the innate and adaptive arms of the immunity.

Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules, whose list is constantly updated to fill the several empty spaces of this puzzle. The recent development of new technologies and computational tools allows to perform a comprehensive and quantitative analysis of the interactions between all of the components of immunity over time.

Here we review the role of the innate immunity in the host response to vaccine antigens and the potential of systems biology in providing relevant and novel insights in the mechanisms of action of vaccines in order to improve their design and effectiveness.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abbas AR, Baldwin D, Ma Y et al. (2005) Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data. Genes Immun 6:319–331.

    Article  PubMed  CAS  Google Scholar 

  • Agrawal S, Agrawal A, Doughty B et al. (2003) Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol 171:4984–4989.

    PubMed  CAS  Google Scholar 

  • Ahmad-Nejad P, Hacker H, Rutz M et al. (2002) Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur J Immunol 32:1958–1968.

    Article  PubMed  CAS  Google Scholar 

  • Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801.

    Article  PubMed  CAS  Google Scholar 

  • Alderson MR, Smith CA, Tough TW et al. (1994) Molecular and biological characterization of human 4-1BB and its ligand. Eur J Immunol 24:2219–2227.

    Article  PubMed  CAS  Google Scholar 

  • Alexopoulou L, Holt AC, Medzhitov R et al. (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732–738.

    Article  PubMed  CAS  Google Scholar 

  • Alexopoulou L, Thomas V, Schnare M et al. (2002) Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat Med 8:878–884.

    PubMed  CAS  Google Scholar 

  • Alizadeh AA and Staudt LM (2000) Genomic-scale gene expression profiling of normal and malignant immune cells. Curr Opin Immunol 12:219–225.

    Article  PubMed  CAS  Google Scholar 

  • Allen A, Obaro S, Bojang K et al. (2003) Variation in Toll-like receptor 4 and susceptibility to group A meningococcal meningitis in Gambian children. Pediatr Infect Dis J 22:1018–1019.

    Article  PubMed  Google Scholar 

  • Alvarez D, Vollmann EH, von Andrian UH (2008) Mechanisms and consequences of dendritic cell migration. Immunity 29:325–342.

    Article  PubMed  CAS  Google Scholar 

  • Andres PG, Howland KC, Nirula A et al. (2004) Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation. Nat Immunol 5:435–442.

    Article  PubMed  CAS  Google Scholar 

  • Aricò E, Wang E, Tornesello ML et al. (2005) Immature monocyte derived dendritic cells gene expression profile in response to Virus-Like Particles stimulation. J Transl Med 3:45

    Article  PubMed  CAS  Google Scholar 

  • Asahi-Ozaki Y, Itamura S, Ichinohe T et al. (2006) Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection. Microbes Infect 8:2706–2714.

    Article  PubMed  CAS  Google Scholar 

  • Assudani D, Cho HI, DeVito N et al. (2008) In vivo expansion, persistence, and function of peptide vaccine-induced CD8 T cells occur independently of CD4 T cells. Cancer Res 68:9892–9899.

    Article  PubMed  CAS  Google Scholar 

  • Bachmann MF, Zinkernagel RM, Oxenius A (1998) Immune responses in the absence of costimulation: viruses know the trick. J Immunol 161:5791–5794.

    PubMed  CAS  Google Scholar 

  • Bakal C, Linding R, Llense F et al. (2008) Phosphorylation networks regulating JNK activity in diverse genetic backgrounds. Science 322:453–456.

    Article  PubMed  CAS  Google Scholar 

  • Baldridge JR and Crane RT (1999) Monophosphoryl lipid A (MPL) formulations for the next generation of vaccines. Methods 19:103–107.

    Article  PubMed  CAS  Google Scholar 

  • Banchereau J and Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252.

    Article  PubMed  CAS  Google Scholar 

  • Banchereau J, Klechevsky E, Schmitt N et al. (2009) Harnessing human dendritic cell subsets to design novel vaccines. Ann N Y Acad Sci 1174:24–32.

    Article  PubMed  CAS  Google Scholar 

  • Banus S, Bottema RW, Siezen CL et al. (2007) Toll-like receptor 4 polymorphism associated with the response to whole-cell pertussis vaccination in children from the KOALA study. Clin Vaccine Immunol 14:1377–1380.

    Article  PubMed  CAS  Google Scholar 

  • Belshe RB, Edwards KM, Vesikari T et al. (2007) Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 356:685–696.

    Article  PubMed  CAS  Google Scholar 

  • Beltinger CP, White PS, Maris JM et al. (1996) Physical mapping and genomic structure of the human TNFR2 gene. Genomics 35:94–100.

    Article  PubMed  CAS  Google Scholar 

  • Beutler B (2004) Inferences, questions and possibilities in Toll-like receptor signalling. Nature 430:257–263.

    Article  PubMed  CAS  Google Scholar 

  • Bhat NK, Thompson CB, Lindsten T et al. (1990) Reciprocal expression of human ETS1 and ETS2 genes during T-cell activation: regulatory role for the protooncogene ETS1. Proc Natl Acad Sci U S A 87:3723–3727.

    Article  PubMed  CAS  Google Scholar 

  • Blumenthal SG, Aichele G, Wirth T et al. (1999) Regulation of the human interleukin-5 promoter by Ets transcription factors. Ets1 and Ets2, but not Elf-1, cooperate with GATA3 and HTLV-I Tax1. J Biol Chem 274:12910–12916.

    Article  PubMed  CAS  Google Scholar 

  • Bochud PY, Bochud M, Telenti A et al. (2007a) Innate immunogenetics: a tool for exploring new frontiers of host defence. Lancet Infect Dis 7:531–542.

    Article  PubMed  CAS  Google Scholar 

  • Bochud PY, Hersberger M, Taffe P et al. (2007b) Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection. AIDS 21:441–446.

    Article  PubMed  CAS  Google Scholar 

  • Bowie A and O’Neill LA (2000) The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleukins and microbial products. J Leukoc Biol 67:508–514.

    PubMed  CAS  Google Scholar 

  • Bowie AG and Unterholzner L (2008) Viral evasion and subversion of pattern-recognition receptor signalling. Nat Rev Immunol 8:911–922.

    Article  PubMed  CAS  Google Scholar 

  • Brass AL, Dykxhoorn DM, Benita Y et al. (2008) Identification of host proteins required for HIV infection through a functional genomic screen. Science 319:921–926.

    Article  PubMed  CAS  Google Scholar 

  • Brightbill HD, Libraty DH, Krutzik SR et al. (1999) Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285:732–736.

    Article  PubMed  CAS  Google Scholar 

  • Bulut Y, Faure E, Thomas L et al. (2001) Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J Immunol 167:987–994.

    PubMed  CAS  Google Scholar 

  • Buonaguro L, Racioppi L, Tornesello ML et al. (2002) Induction of neutralizing antibodies and CTLs in Balb/c mice immunized with Virus-like Particles presenting a gp120 molecule from a HIV-1 isolate of clade A (HIV-VLPAs). Antiviral Res 54:189–201.

    Article  PubMed  CAS  Google Scholar 

  • Buonaguro L, Visciano ML, Tornesello ML et al. (2005) Induction of systemic and mucosal cross-clade neutralizing antibodies in BALB/c mice immunized with human immunodeficiency virus type 1 clade A virus-like particles administered by different routes of inoculation. J Virol 79:7059–7067.

    Article  PubMed  CAS  Google Scholar 

  • Buonaguro L, Tornesello ML, Tagliamonte M et al. (2006) Baculovirus-derived human immunodeficiency virus type 1 virus-like particles activate dendritic cells and induce ex vivo T-cell responses. J Virol 80:9134–9143.

    Article  PubMed  CAS  Google Scholar 

  • Buonaguro L, Devito C, Tornesello ML et al. (2007) DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity. Vaccine 25:5968–5977.

    Article  PubMed  CAS  Google Scholar 

  • Buonaguro L, Monaco A, Arico E et al. (2008) Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation. BMC Bioinformatics 9(Suppl 2):S5

    Article  PubMed  CAS  Google Scholar 

  • Buonaguro L, Tornesello ML, Gallo RC et al. (2009a) Th2 polarization in peripheral blood mononuclear cells from human immunodeficiency virus (HIV)-infected subjects, as activated by HIV virus-like particles. J Virol 83:304–313.

    Article  PubMed  CAS  Google Scholar 

  • Buonaguro L, Tornesello ML, Jewis GK et al. (2009b) Short communication: limited induction of IL-10 in PBMCs from HIV-infected subjects treated with HIV-VLPs. AIDS Res Hum Retroviruses 25:819–822.

    Article  PubMed  CAS  Google Scholar 

  • Ceol A, Chatr AA, Licata L et al. (2010) MINT, the molecular interaction database: 2009 update. Nucleic Acids Res 38:D532–D539.

    Article  PubMed  CAS  Google Scholar 

  • Chatr-aryamontri A, Ceol A, Peluso D et al. (2009) VirusMINT: a viral protein interaction database. Nucleic Acids Res 37:D669–D673.

    Article  PubMed  CAS  Google Scholar 

  • Chaussabel D, Quinn C, Shen J et al. (2008) A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus. Immunity 29:150–164.

    Article  PubMed  CAS  Google Scholar 

  • de Chassey B, Navratil V, Tafforeau L et al. (2008) Hepatitis C virus infection protein network. Mol Syst Biol 4:230

    PubMed  Google Scholar 

  • de la Torre MS, Torres C, Nieto G et al. (2008) Vitamin D receptor gene haplotypes and susceptibility to HIV-1 infection in injection drug users. J Infect Dis 197:405–410.

    Article  PubMed  CAS  Google Scholar 

  • den Dunnen J, Gringhuis SI, Geijtenbeek TB (2009) Innate signaling by the C-type lectin DC-SIGN dictates immune responses. Cancer Immunol Immunother 58:1149–1157.

    Article  CAS  Google Scholar 

  • Dhiman N, Ovsyannikova IG, Vierkant RA et al. (2008) Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results. Vaccine 26:1731–1736.

    Article  PubMed  CAS  Google Scholar 

  • Dickinson AM and Holler E (2008) Polymorphisms of cytokine and innate immunity genes and GVHD. Best Pract Res Clin Haematol 21:149–164.

    Article  PubMed  CAS  Google Scholar 

  • Didierlaurent A, Brissoni B, Velin D et al. (2006) Tollip regulates proinflammatory responses to interleukin-1 and lipopolysaccharide. Mol Cell Biol 26:735–742.

    Article  PubMed  CAS  Google Scholar 

  • Diebold SS (2008) Recognition of viral single-stranded RNA by Toll-like receptors. Adv Drug Deliv Rev 60:813–823.

    Article  PubMed  CAS  Google Scholar 

  • Diebold SS, Kaisho T, Hemmi H et al. (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529–1531.

    Article  PubMed  CAS  Google Scholar 

  • Dillon S, Agrawal A, van DT et al. (2004) A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J Immunol 172:4733–4743.

    Google Scholar 

  • Dillon S, Agrawal S, Banerjee K et al. (2006) Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J Clin Invest 116:916–928.

    Article  PubMed  CAS  Google Scholar 

  • Draper SJ and Heeney JL (2010) Viruses as vaccine vectors for infectious diseases and cancer. Nat Rev Microbiol 8:62–73.

    Article  PubMed  CAS  Google Scholar 

  • Driscoll T, Dyer MD, Murali TM et al. (2009) PIG--the pathogen interaction gateway. Nucleic Acids Res 37:D647–D650.

    Article  PubMed  CAS  Google Scholar 

  • Elkon R, Linhart C, Halperin Y et al. (2007) Functional genomic delineation of TLR-induced transcriptional networks. BMC Genomics 8:394

    Article  PubMed  Google Scholar 

  • Ferwerda B, McCall MB, Alonso S et al. (2007) TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proc Natl Acad Sci U S A 104:16645–16650.

    Article  PubMed  Google Scholar 

  • Ferwerda B, McCall MB, Verheijen K et al. (2008) Functional consequences of toll-like receptor 4 polymorphisms. Mol Med 14:346–352.

    Article  PubMed  CAS  Google Scholar 

  • Fraser CK, Diener KR, Brown MP et al. (2007) Improving vaccines by incorporating immunological coadjuvants. Expert Rev Vaccines 6:559–578.

    Article  PubMed  CAS  Google Scholar 

  • Gallant S and Gilkeson G (2006) ETS transcription factors and regulation of immunity. Arch Immunol Ther Exp (Warsz ) 54:149–163.

    Article  CAS  Google Scholar 

  • Gardy JL, Lynn DJ, Brinkman FS et al. (2009) Enabling a systems biology approach to immunology: focus on innate immunity. Trends Immunol 30:249–262.

    Article  PubMed  CAS  Google Scholar 

  • Gaucher D, Therrien R, Kettaf N et al. (2008) Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses. J Exp Med 205:3119–3131.

    Article  PubMed  CAS  Google Scholar 

  • Geijtenbeek TB, van Vliet SJ, Engering A et al. (2004) Self- and nonself-recognition by C-type lectins on dendritic cells. Annu Rev Immunol 22:33–54.

    Article  PubMed  CAS  Google Scholar 

  • Gelman AE, Zhang J, Choi Y et al. (2004) Toll-like receptor ligands directly promote activated CD4+ T cell survival. J Immunol 172:6065–6073.

    PubMed  CAS  Google Scholar 

  • Georgel P, Macquin C, Bahram S (2009) The heterogeneous allelic repertoire of human toll-like receptor (TLR) genes. PLoS One 4:e7803

    Article  PubMed  CAS  Google Scholar 

  • Germain RN (2004) An innately interesting decade of research in immunology. Nat Med 10:1307–1320.

    Article  PubMed  CAS  Google Scholar 

  • Gilliet M, Cao W, Liu YJ (2008) Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol 8:594–606.

    Article  PubMed  CAS  Google Scholar 

  • Gluck R, Moser C, Metcalfe IC (2004) Influenza virosomes as an efficient system for adjuvanted vaccine delivery. Expert Opin Biol Ther 4:1139–1145.

    Article  PubMed  Google Scholar 

  • Groux H, O’Garra A, Bigler M et al. (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389:737–742.

    Article  PubMed  CAS  Google Scholar 

  • Hayashi F, Smith KD, Ozinsky A et al. (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410:1099–1103.

    Article  PubMed  CAS  Google Scholar 

  • Heil F, Hemmi H, Hochrein H et al. (2004) Species-specific recognition of single-stranded RNA via toll- like receptor 7 and 8. Science 303:1526–1529.

    Article  PubMed  CAS  Google Scholar 

  • Hemmi H, Takeuchi O, Kawai T et al. (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408:740–745.

    Article  PubMed  CAS  Google Scholar 

  • Hemmi H, Kaisho T, Takeuchi O et al. (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3:196–200.

    Article  PubMed  CAS  Google Scholar 

  • Hemmi H, Kaisho T, Takeda K et al. (2003) The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets. J Immunol 170:3059–3064.

    PubMed  CAS  Google Scholar 

  • Heng TS and Painter MW (2008) The Immunological Genome Project: networks of gene expression in immune cells. Nat Immunol 9:1091–1094.

    Article  PubMed  CAS  Google Scholar 

  • Hervas-Stubbs S, Olivier A, Boisgerault F et al. (2007) TLR3 ligand stimulates fully functional memory CD8+ T cells in the absence of CD4+ T-cell help. Blood 109:5318–5326.

    Article  PubMed  CAS  Google Scholar 

  • Hijikata A, Kitamura H, Kimura Y et al. (2007) Construction of an open-access database that integrates cross-reference information from the transcriptome and proteome of immune cells. Bioinformatics 23:2934–2941.

    Article  PubMed  CAS  Google Scholar 

  • Hoek KL, Carlesso G, Clark ES et al. (2009) Absence of mature peripheral B cell populations in mice with concomitant defects in B cell receptor and BAFF-R signaling. J Immunol 183:5630–5643.

    Article  PubMed  CAS  Google Scholar 

  • Holzer BR, Hatz C, Schmidt-Sissolak D et al. (1996) Immunogenicity and adverse effects of inactivated virosome versus alum-adsorbed hepatitis A vaccine: a randomized controlled trial. Vaccine 14:982–986.

    Article  PubMed  CAS  Google Scholar 

  • Houghton M and Abrignani S (2005) Prospects for a vaccine against the hepatitis C virus. Nature 436:961–966.

    Article  PubMed  CAS  Google Scholar 

  • Hu J, Sealfon SC, Hayot F et al. (2007) Chromosome-specific and noisy IFNB1 transcription in individual virus-infected human primary dendritic cells. Nucleic Acids Res 35:5232–5241.

    Article  PubMed  CAS  Google Scholar 

  • Huleatt JW, Nakaar V, Desai P et al. (2008) Potent immunogenicity and efficacy of a universal influenza vaccine candidate comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand flagellin. Vaccine 26:201–214.

    Article  PubMed  CAS  Google Scholar 

  • Inohara, Chamaillard, McDonald C et al. (2005) NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. Annu Rev Biochem 74:355–383.

    Article  PubMed  CAS  Google Scholar 

  • Ishii KJ and Akira S (2007) Toll or toll-free adjuvant path toward the optimal vaccine development. J Clin Immunol 27:363–371.

    Article  PubMed  CAS  Google Scholar 

  • Janeway CA, Jr. and Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216.

    Article  PubMed  CAS  Google Scholar 

  • Jenner RG and Young RA (2005) Insights into host responses against pathogens from transcriptional profiling. Nat Rev Microbiol 3:281–294.

    Article  PubMed  CAS  Google Scholar 

  • Johnston D, Zaidi B, Bystryn JC (2007) TLR7 imidazoquinoline ligand 3M-019 is a potent adjuvant for pure protein prototype vaccines. Cancer Immunol Immunother 56:1133–1141.

    Article  PubMed  CAS  Google Scholar 

  • Kaech SM, Wherry EJ, Ahmed R (2002) Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol 2:251–262.

    Article  PubMed  CAS  Google Scholar 

  • Kang SM and Compans RW (2009) Host responses from innate to adaptive immunity after vaccination: molecular and cellular events. Mol Cells 27:5–14.

    Article  PubMed  CAS  Google Scholar 

  • Kawabe T, Naka T, Yoshida K et al. (1994) The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation. Immunity 1:167–178.

    Article  PubMed  CAS  Google Scholar 

  • Keam SJ and Harper DM (2008) Human papillomavirus types 16 and 18 vaccine (recombinant, AS04 adjuvanted, adsorbed) [Cervarix]. Drugs 68:359–372.

    Article  PubMed  CAS  Google Scholar 

  • Khan WN (2009) B cell receptor and BAFF receptor signaling regulation of B cell homeostasis. J Immunol 183:3561–3567.

    Article  PubMed  CAS  Google Scholar 

  • Kimberlin DW and Whitley RJ (2007) Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med 356:1338–1343.

    Article  PubMed  CAS  Google Scholar 

  • Kimman TG, Banus S, Reijmerink N et al. (2008) Association of interacting genes in the toll-like receptor signaling pathway and the antibody response to pertussis vaccination. PLoS One 3:e3665

    Article  PubMed  CAS  Google Scholar 

  • Korb M, Rust AG, Thorsson V et al. (2008) The Innate Immune Database (IIDB). BMC Immunol 9:7

    Article  PubMed  CAS  Google Scholar 

  • Korber BT, Letvin NL, Haynes BF (2009) T-cell vaccine strategies for human immunodeficiency virus, the virus with a thousand faces. J Virol 83:8300–8314.

    Article  PubMed  CAS  Google Scholar 

  • Kozlow EJ, Wilson GL, Fox CH et al. (1993) Subtractive cDNA cloning of a novel member of the Ig gene superfamily expressed at high levels in activated B lymphocytes. Blood 81:454–461.

    PubMed  CAS  Google Scholar 

  • Krieg AM (2006) Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov 5:471–484.

    Article  PubMed  CAS  Google Scholar 

  • Krieg AM (2008) Toll-like receptor 9 (TLR9) agonists in the treatment of cancer. Oncogene 27:161–167.

    Article  PubMed  CAS  Google Scholar 

  • Krishnan MN, Ng A, Sukumaran B et al. (2008) RNA interference screen for human genes associated with West Nile virus infection. Nature 455:242–245.

    Article  PubMed  CAS  Google Scholar 

  • Kwissa M, Amara RR, Robinson HL et al. (2007a) Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus. J Exp Med 204:2733–2746.

    Article  PubMed  CAS  Google Scholar 

  • Kwissa M, Kasturi SP, Pulendran B (2007b) The science of adjuvants. Expert Rev Vaccines 6:673–684.

    Article  PubMed  CAS  Google Scholar 

  • Lafaille JJ (1998) The role of helper T cell subsets in autoimmune diseases. Cytokine Growth Factor Rev 9:139–151.

    Article  PubMed  CAS  Google Scholar 

  • Lahiri A, Das P, Chakravortty D (2008) Engagement of TLR signaling as adjuvant: towards smarter vaccine and beyond. Vaccine 26:6777–6783.

    Article  PubMed  CAS  Google Scholar 

  • Latz E, Franko J, Golenbock DT et al. (2004a) Haemophilus influenzae type b-outer membrane protein complex glycoconjugate vaccine induces cytokine production by engaging human toll-like receptor 2 (TLR2) and requires the presence of TLR2 for optimal immunogenicity. J Immunol 172:2431–2438.

    PubMed  CAS  Google Scholar 

  • Latz E, Schoenemeyer A, Visintin A et al. (2004b) TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol 5:190–198.

    Article  PubMed  CAS  Google Scholar 

  • Leber JH, Crimmins GT, Raghavan S et al. (2008) Distinct TLR- and NLR-mediated transcriptional responses to an intracellular pathogen. PLoS Pathog 4:e6

    Article  PubMed  CAS  Google Scholar 

  • Liu YJ (2005) IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol 23:275–306.

    Article  PubMed  CAS  Google Scholar 

  • Longhi MP, Trumpfheller C, Idoyaga J et al. (2009) Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med 206:1589–1602.

    Article  PubMed  CAS  Google Scholar 

  • Lorenz E, Mira JP, Frees KL et al. (2002) Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch Intern Med 162:1028–1032.

    Article  PubMed  CAS  Google Scholar 

  • Lund JM, Alexopoulou L, Sato A et al. (2004) Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci U S A 101:5598–5603.

    Article  PubMed  CAS  Google Scholar 

  • Lynn DJ, Winsor GL, Chan C et al. (2008) InnateDB: facilitating systems-level analyses of the mammalian innate immune response. Mol Syst Biol 4:218

    Article  PubMed  CAS  Google Scholar 

  • Ma R, Du JL, Huang J et al. (2007) Additive effects of CpG ODN and R-848 as adjuvants on augmenting immune responses to HBsAg vaccination. Biochem Biophys Res Commun 361:537–542.

    Article  PubMed  CAS  Google Scholar 

  • Magistrelli G, Jeannin P, Elson G et al. (1999) Identification of three alternatively spliced variants of human CD28 mRNA. Biochem Biophys Res Commun 259:34–37.

    Article  PubMed  CAS  Google Scholar 

  • McCaffrey RL, Fawcett P, O’Riordan M et al. (2004) A specific gene expression program triggered by Gram-positive bacteria in the cytosol. Proc Natl Acad Sci U S A 101:11386–11391.

    Article  PubMed  CAS  Google Scholar 

  • McGuirk P and Mills KH (2002) Pathogen-specific regulatory T cells provoke a shift in the Th1/Th2 paradigm in immunity to infectious diseases. Trends Immunol 23:450–455.

    Article  PubMed  CAS  Google Scholar 

  • Mikszta JA, Dekker JP, III, Harvey NG et al. (2006) Microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine. Infect Immun 74:6806–6810.

    Article  PubMed  CAS  Google Scholar 

  • Misch EA and Hawn TR (2008) Toll-like receptor polymorphisms and susceptibility to human disease. Clin Sci (Lond) 114:347–360.

    Article  Google Scholar 

  • Miyairi I and DeVincenzo JP (2008) Human genetic factors and respiratory syncytial virus disease severity. Clin Microbiol Rev 21:686–703.

    Article  PubMed  CAS  Google Scholar 

  • Monaco A, Marincola FM, Sabatino M et al. (2009) Molecular immune signatures of HIV-1 vaccines in human PBMCs. FEBS Lett 583:3004–3008.

    Article  PubMed  CAS  Google Scholar 

  • Monath TP (2005) Yellow fever vaccine. Expert Rev Vaccines 4:553–574.

    Article  PubMed  CAS  Google Scholar 

  • Monie TP, Bryant CE, Gay NJ (2009) Activating immunity: lessons from the TLRs and NLRs. Trends Biochem Sci 34:553–561.

    Article  PubMed  CAS  Google Scholar 

  • Moser M and Murphy KM (2000) Dendritic cell regulation of TH1-TH2 development. Nat Immunol 1:199–205.

    Article  PubMed  CAS  Google Scholar 

  • Mowen KA and Glimcher LH (2004) Signaling pathways in Th2 development. Immunol Rev 202:203–222.

    Article  PubMed  CAS  Google Scholar 

  • Navabi H, Jasani B, Reece A et al. (2009) A clinical grade poly I:C-analogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro. Vaccine 27:107–115.

    Article  PubMed  CAS  Google Scholar 

  • Navratil V, de CB, Meyniel L et al. (2009) VirHostNet: a knowledge base for the management and the analysis of proteome-wide virus-host interaction networks. Nucleic Acids Res 37:D661–D668.

    Google Scholar 

  • Nguyen TH, Mai NL, Le TP et al. (2009) Toll-like receptor 4 (TLR4) and typhoid fever in Vietnam. PLoS One 4:e4800.

    Article  PubMed  CAS  Google Scholar 

  • O’Garra A and Robinson D (2004) Development and function of T helper 1 cells. Adv Immunol 83:133–162.

    Article  PubMed  Google Scholar 

  • O’Garra A and Vieira P (2004) Regulatory T cells and mechanisms of immune system control. Nat Med 10:801–805.

    Article  PubMed  CAS  Google Scholar 

  • Oda K and Kitano H (2006) A comprehensive map of the toll-like receptor signaling network. Mol Syst Biol 2:2006.

    Article  Google Scholar 

  • Ogus AC, Yoldas B, Ozdemir T et al. (2004) The Arg753GLn polymorphism of the human toll-like receptor 2 gene in tuberculosis disease. Eur Respir J 23:219–223.

    Article  PubMed  CAS  Google Scholar 

  • Ott G, Barchfeld GL, Chernoff D et al. (1995) MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol 6:277–296.

    Article  PubMed  CAS  Google Scholar 

  • Ovsyannikova IG, Dhiman N, Haralambieva IH et al. (2010) Rubella vaccine-induced cellular immunity: evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes. Hum Genet 127:207–221.

    Article  PubMed  CAS  Google Scholar 

  • Ozinsky A, Underhill DM, Fontenot JD et al. (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci U S A 97:13766–13771.

    Article  PubMed  CAS  Google Scholar 

  • Pancharoen C, Mekmullica J, Thisyakorn U et al. (2005) Reduced-dose intradermal vaccination against hepatitis A with an aluminum-free vaccine is immunogenic and can lower costs. Clin Infect Dis 41:1537–1540.

    Article  PubMed  Google Scholar 

  • Pasare C and Medzhitov R (2005) Toll-like receptors: linking innate and adaptive immunity. Adv Exp Med Biol 560:11–18.

    Article  PubMed  CAS  Google Scholar 

  • Pashine A, Valiante NM, Ulmer JB (2005) Targeting the innate immune response with improved vaccine adjuvants. Nat Med 11:S63–S68.

    Article  PubMed  CAS  Google Scholar 

  • Pine SO, McElrath MJ, Bochud PY (2009) Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals. AIDS 23:2387–2395.

    Article  PubMed  CAS  Google Scholar 

  • Pitti RM, Marsters SA, Lawrence DA et al. (1998) Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 396:699–703.

    Article  PubMed  CAS  Google Scholar 

  • Plotkin SA (2005) Vaccines: past, present and future. Nat Med 11:S5–S11.

    Article  PubMed  CAS  Google Scholar 

  • Poltorak A, He X, Smirnova I et al. (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088.

    Article  PubMed  CAS  Google Scholar 

  • Potti A, Dressman HK, Bild A et al. (2006) Genomic signatures to guide the use of chemotherapeutics. Nat Med 12:1294–1300.

    Article  PubMed  CAS  Google Scholar 

  • Pulendran B and Ahmed R (2006) Translating innate immunity into immunological memory: implications for vaccine development. Cell 124:849–863.

    Article  PubMed  CAS  Google Scholar 

  • Querec T, Bennouna S, Alkan S et al. (2006) Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J Exp Med 203:413–424.

    Article  PubMed  Google Scholar 

  • Querec TD, Akondy RS, Lee EK et al. (2009) Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol 10:116–125.

    Article  PubMed  CAS  Google Scholar 

  • Ramilo O, Allman W, Chung W et al. (2007) Gene expression patterns in blood leukocytes discriminate patients with acute infections. Blood 109:2066–2077.

    Article  PubMed  CAS  Google Scholar 

  • Rappuoli R (2004) From Pasteur to genomics: progress and challenges in infectious diseases. Nat Med 10:1177–1185.

    Article  PubMed  CAS  Google Scholar 

  • Rappuoli R (2007) Bridging the knowledge gaps in vaccine design. Nat Biotechnol 25:1361–1366.

    Article  PubMed  CAS  Google Scholar 

  • Read RC, Pullin J, Gregory S et al. (2001) A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease. J Infect Dis 184:640–642.

    Article  PubMed  CAS  Google Scholar 

  • Redecke V, Hacker H, Datta SK et al. (2004) Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J Immunol 172:2739–2743.

    PubMed  CAS  Google Scholar 

  • Reed SG, Bertholet S, Coler RN et al. (2009) New horizons in adjuvants for vaccine development. Trends Immunol 30:23–32.

    Article  PubMed  CAS  Google Scholar 

  • Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S et al. (2009) Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand. N Engl J Med 361:2209–2220.

    Google Scholar 

  • Rezazadeh M, Hajilooi M, Rafiei A et al. (2006) TLR4 polymorphism in Iranian patients with brucellosis. J Infect 53:206–210.

    Article  PubMed  CAS  Google Scholar 

  • Ricciardi-Castagnoli P and Granucci F (2002) Opinion: Interpretation of the complexity of innate immune responses by functional genomics. Nat Rev Immunol 2:881–889.

    Article  PubMed  CAS  Google Scholar 

  • Richter JD and Sonenberg N (2005) Regulation of cap-dependent translation by eIF4E inhibitory proteins. Nature 433:477–480.

    Article  PubMed  CAS  Google Scholar 

  • Robbins JB, Schneerson R, Szu SC (1995) Perspective: hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum. J Infect Dis 171:1387–1398.

    Article  PubMed  CAS  Google Scholar 

  • Robbins JB, Schneerson R, Szu SC (1996) Hypothesis: how licensed vaccines confer protective immunity. Adv Exp Med Biol 397:169–182.

    PubMed  CAS  Google Scholar 

  • Ron D and Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8:519–529.

    Article  PubMed  CAS  Google Scholar 

  • Ryan ET and Calderwood SB (2000) Cholera vaccines. Clin Infect Dis 31:561–565.

    Article  PubMed  CAS  Google Scholar 

  • Sallberg M, Frelin L, Weiland O (2009) DNA vaccine therapy for chronic hepatitis C virus (HCV) infection: immune control of a moving target. Expert Opin Biol Ther 9:805–815.

    Article  PubMed  CAS  Google Scholar 

  • Santos AP, Matos DC, Bertho AL et al. (2008) Detection of Th1/Th2 cytokine signatures in yellow fever 17DD first-time vaccinees through ELISpot assay. Cytokine 42:152–155.

    Article  PubMed  CAS  Google Scholar 

  • Sato Y, Goto Y, Narita N et al. (2009) Cancer Cells Expressing Toll-like Receptors and the Tumor Microenvironment. Cancer Microenviron 2(Suppl 1):205–214.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt WM, Spiel AO, Jilma B et al. (2009) In vivo profile of the human leukocyte microRNA response to endotoxemia. Biochem Biophys Res Commun 380:437–441.

    Article  PubMed  CAS  Google Scholar 

  • Schonbeck U and Libby P (2001) The CD40/CD154 receptor/ligand dyad. Cell Mol Life Sci 58:4–43.

    Article  PubMed  CAS  Google Scholar 

  • Schroder NW and Schumann RR (2005) Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis 5:156–164.

    Article  PubMed  Google Scholar 

  • Shimazu R, Akashi S, Ogata H et al. (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 189:1777–1782.

    Article  PubMed  CAS  Google Scholar 

  • Sioud M (2009) Does our current understanding of immune tolerance, autoimmunity, and immunosuppressive mechanisms facilitate the design of efficient cancer vaccines? Scand J Immunol 70:516–525.

    Article  PubMed  CAS  Google Scholar 

  • Smirnova I, Mann N, Dols A et al. (2003) Assay of locus-specific genetic load implicates rare Toll-like receptor 4 mutations in meningococcal susceptibility. Proc Natl Acad Sci U S A 100:6075–6080.

    Article  PubMed  CAS  Google Scholar 

  • Sorlie T, Perou CM, Tibshirani R et al. (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874.

    Article  PubMed  CAS  Google Scholar 

  • Speiser DE, Lienard D, Rufer N et al. (2005) Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J Clin Invest 115:739–746.

    PubMed  CAS  Google Scholar 

  • Stahl S, Fung E, Adams C et al. (2009) Proteomics and pathway analysis identifies JNK signaling as critical for high linear energy transfer radiation-induced apoptosis in non-small lung cancer cells. Mol Cell Proteomics 8:1117–1129.

    Article  PubMed  CAS  Google Scholar 

  • Stephan MT, Ponomarev V, Brentjens RJ et al. (2007) T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection. Nat Med 13:1440–1449.

    Article  PubMed  CAS  Google Scholar 

  • Sun HJ, Xu X, Wang XL et al. (2006) Transcription factors Ets2 and Sp1 act synergistically with histone acetyltransferase p300 in activating human interleukin-12 p40 promoter. Acta Biochim Biophys Sin (Shanghai) 38:194–200.

    Article  CAS  Google Scholar 

  • Takeda K and Akira S (2007) Toll-like receptors. Curr Protoc Immunol Chapter 14:Unit PMID: 18432983 DOI: 10.1002/0471142735.im1412s77.

  • Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Annu Rev Immunol 21:335–376.

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi O, Kawai T, Muhlradt PF et al. (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 13:933–940.

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi O, Sato S, Horiuchi T et al. (2002) Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 169:10–14.

    PubMed  CAS  Google Scholar 

  • Tanabe M, Kurita-Taniguchi M, Takeuchi K et al. (2003) Mechanism of up-regulation of human Toll-like receptor 3 secondary to infection of measles virus-attenuated strains. Biochem Biophys Res Commun 311:39–48.

    Article  PubMed  CAS  Google Scholar 

  • Thomas V and Fikrig E (2002) The Lyme disease vaccine takes its toll. Vector Borne Zoonotic Dis 2:217–222.

    Article  PubMed  Google Scholar 

  • Tong NK, Beran J, Kee SA et al. (2005) Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients. Kidney Int 68:2298–2303.

    Article  PubMed  CAS  Google Scholar 

  • Tsuji S, Matsumoto M, Takeuchi O et al. (2000) Maturation of human dendritic cells by cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guerin: involvement of toll-like receptors. Infect Immun 68:6883–6890.

    Article  PubMed  CAS  Google Scholar 

  • Uehori J, Matsumoto M, Tsuji S et al. (2003) Simultaneous blocking of human Toll-like receptors 2 and 4 suppresses myeloid dendritic cell activation induced by Mycobacterium bovis bacillus Calmette-Guerin peptidoglycan. Infect Immun 71:4238–4249.

    Article  PubMed  CAS  Google Scholar 

  • van Manen D, Rits MA, Beugeling C et al. (2008) The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection. PLoS Pathog 4:e18.

    Article  PubMed  CAS  Google Scholar 

  • Van DP, Oosterhuis-Kafeja F, Van der WM et al. (2009) Safety and efficacy of a novel micro­needle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine 27:454–459.

    Article  Google Scholar 

  • Vasilescu C, Rossi S, Shimizu M et al. (2009) MicroRNA fingerprints identify miR-150 as a plasma prognostic marker in patients with sepsis. PLoS One 4:e7405

    Article  PubMed  CAS  Google Scholar 

  • Velez DR, Wejse C, Stryjewski ME et al. (2010) Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans. Hum Genet 127:65–73.

    Article  PubMed  CAS  Google Scholar 

  • Villadangos JA and Young L (2008) Antigen-presentation properties of plasmacytoid dendritic cells. Immunity 29:352–361.

    Article  PubMed  CAS  Google Scholar 

  • von Andrian UH and Mempel TR (2003) Homing and cellular traffic in lymph nodes. Nat Rev Immunol 3:867–878.

    Article  CAS  Google Scholar 

  • Wang Z, Gerstein M, Snyder M (2009) RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10:57–63.

    Article  PubMed  CAS  Google Scholar 

  • Wille-Reece U, Flynn BJ, Lore K et al. (2006) Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. J Exp Med 203:1249–1258.

    Article  PubMed  CAS  Google Scholar 

  • Wurfel MM, Gordon AC, Holden TD et al. (2008) Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. Am J Respir Crit Care Med 178:710–720.

    Article  PubMed  CAS  Google Scholar 

  • Yim JJ, Lee HW, Lee HS et al. (2006) The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans. Genes Immun 7:150–155.

    Article  PubMed  CAS  Google Scholar 

  • Yin JQ, Zhao RC, Morris KV (2008) Profiling microRNA expression with microarrays. Trends Biotechnol 26:70–76.

    Article  PubMed  CAS  Google Scholar 

  • Yoneyama M and Fujita T (2009) RNA recognition and signal transduction by RIG-I-like receptors. Immunol Rev 227:54–65.

    Article  PubMed  CAS  Google Scholar 

  • Yoneyama M, Kikuchi M, Natsukawa T et al. (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5:730-737.

    Article  PubMed  CAS  Google Scholar 

  • Yoneyama M, Kikuchi M, Matsumoto K et al. (2005) Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 175:2851–2858.

    PubMed  CAS  Google Scholar 

  • Yoshida A, Inagawa H, Kohchi C et al. (2009) The role of toll-like receptor 2 in survival strategies of Mycobacterium tuberculosis in macrophage phagosomes. Anticancer Res 29:907–910.

    PubMed  CAS  Google Scholar 

  • Zhou R, Hu G, Liu J et al. (2009) NF-kappaB p65-dependent transactivation of miRNA genes following Cryptosporidium parvum infection stimulates epithelial cell immune responses. PLoS Pathog 5:e1000681.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lab. Mol Biology and Viral Oncogenesis and AIDS Reference Center, Istituto Nazionale Tumori “Fond. G. Pascale”, Via Mariano Semmola, 1, 80131, Naples, Italy

    L. Buonaguro

Authors
  1. F. M. Buonaguro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. L. Tornesello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Buonaguro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Buonaguro .

Editor information

Editors and Affiliations

  1. Clinical Center, Dept. Transfusion Medicine, National Institute of Health (NIH), Center Drive 10, Bethesda, 20892-1502, Maryland, USA

    Francesco M. Marincola

  2. National Institutes of Health Bldg 10, Bethesda, 20892, Maryland, USA

    Ena Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Buonaguro, F.M., Tornesello, M.L., Buonaguro, L. (2011). Immune Signatures and Systems Biology of Vaccines. In: Marincola, F., Wang, E. (eds) Immunologic Signatures of Rejection. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7219-4_10

Download citation

Publish with us

Policies and ethics

Search

Navigation