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The Immunomodulatory Glycan LNFPIII/Lewis X Functions As a Potent Adjuvant for Protein Antigens

  • Chapter
Vaccine Adjuvants

Part of the book series: Infectious Disease ((ID))

Abstract

There has been tremendous effort aimed at developing adjuvants that promote proinflammatory and/or strong cell-mediated immunity; many are discussed in this book. Interestingly, little effort is being placed on development of adjuvants that promote T helper (Th)2-type antibody responses. In part, this may be because alum has proven to be a safe, well-tolerated adjuvant that does bias the immune response in vaccine recipients toward Th2-type responses (1, 2). Additionally, it may because of the perception that Th2-biased immune responses will not provide protection, or that they will not elicit strong cell-mediated responses to vaccine antigens, which is generally true for viral vaccines. However, there are disease situations in which driving Th2 responses is warranted, in particular for helminth infections, many of which require Th2-type responses for immune elimination of parasites (3–5). The second major category would be for preventive and/or therapeutic vaccines for proinflammatory-based autoimmune diseases. This category of diseases is increasing dramatically in humans and their pets. Clearly the use of adjuvants, which drive Th2-biased and/or anti-inflammatory responses, would be beneficial here. In fact, the tremendous increase in proinflammatory autoimmune diseases suggests that it is prudent to limit exposure to strong proinflammatory driving adjuvants and vaccines that promote Th1-type responses.

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References

  1. Lindblad EB. Aluminium compounds for use in vaccines. Immunol Cell Biol 2004;82:497.

    Article  PubMed  CAS  Google Scholar 

  2. Lindblad EB. Aluminium adjuvants—in retrospect and prospect. Vaccine 2004;22:3658.

    Article  PubMed  CAS  Google Scholar 

  3. Bancroft AJ, Artis D, Donaldson DD, Sypek JP, Grencis RK. Gastrointestinal nematode expulsion in IL-4 knockout mice is IL-13 dependent. Eur J Immunol 2000;30:2083.

    Article  PubMed  CAS  Google Scholar 

  4. Madden KB, Urban JF Jr, Ziltener HJ, et al. Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. J Immunol 1991;147:1387.

    PubMed  CAS  Google Scholar 

  5. Urban JF Jr, Maliszewski CR, Madden KB, Katona IM, Finkelman FD. IL-4 treatment can cure established gastrointestinal nematode infections in immunocompetent and immunodeficient mice. J Immunol 1995;154:4675.

    PubMed  CAS  Google Scholar 

  6. Finkelman FD, Urban JF Jr. The other side of the coin: the protective role of the TH2 cytokines. J Allergy Clin Immunol 2001;107:772.

    Article  PubMed  CAS  Google Scholar 

  7. Rogerie F, Gallissot MC, et al. Sex-dependent neutralizing humoral response to Schistosoma mansoni 28GST antigen in infected human populations. J Infect Dis 2000;181:1855.

    Article  PubMed  Google Scholar 

  8. Urban JF Jr, Fayer R, Sullivan C, et al. Local TH1 and TH2 responses to parasitic infection in the intestine: regulation by IFN-gamma and IL-4. Vet Immunol Immunopathol 1996;54:337.

    Article  PubMed  CAS  Google Scholar 

  9. Urban JF Jr, Schopf L, Morris SC, et al. Stat6 signaling promotes protective immunity against Trichinella spiralis through a mast cell-and T cell-dependent mechanism. J Immunol 2000;164:2046.

    PubMed  CAS  Google Scholar 

  10. Fallon PG, Fookes RE, Wharton GA. Temporal differences in praziquantel-and oxamniquine-induced tegumental damage to adult Schistosoma mansoni: implications for drug-antibody synergy. Parasitology 112 1996(Pt 1):47.

    Article  PubMed  CAS  Google Scholar 

  11. Jankovic D, Sher A, Yap G. Th1/Th2 effector choice in parasitic infection: decision making by committee. Curr Opin Immunol 2001;13:403.

    Article  PubMed  CAS  Google Scholar 

  12. O’Garra A. Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 1998;8:275.

    Article  PubMed  CAS  Google Scholar 

  13. Vella AT, Pearce EJ. CD4+ Th2 response induced by Schistosoma mansoni eggs develops rapidly, through an early, transient, Th0-like stage. J Immunol 1992;148:2283

    PubMed  CAS  Google Scholar 

  14. Cook GA, Metwali A, Blum A, Mathew R, Weinstock JV. Lymphokine expression in granulomas of Schistosoma mansoni-infected mice. Cell Immunol 1993;152:49.

    Article  PubMed  CAS  Google Scholar 

  15. van der Kleij D, Latz E, Brouwers JF, et al. A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates toll-like receptor 2 and affects immune polarization. J Biol Chem 2002;277:48122.

    Article  PubMed  Google Scholar 

  16. Velupillai P, dos Reis EA, dos Reis MG, Harn DA. Lewis(x)-containing oligosaccharide attenuates schistosome egg antigen-induced immune depression in human schistosomiasis. Hum Immunol 2000;61:225.

    Article  PubMed  CAS  Google Scholar 

  17. Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med 1991;173:159.

    Article  PubMed  CAS  Google Scholar 

  18. Grzych JM, Pearce E, Cheever A, et al. Egg deposition is the major stimulus for the production of Th2 cytokines in murine schistosomiasis mansoni. J Immunol 1991;146:1322.

    PubMed  CAS  Google Scholar 

  19. Henderson GS, Conary JT, Summar M, McCurley TL, Colley DG. In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. I. IL-4 mRNA, not IL-2 mRNA, is abundant in the granulomatous livers, mesenteric lymph nodes, and spleens of infected mice. J Immunol 1991;147:992.

    PubMed  CAS  Google Scholar 

  20. Ko AI, Drager UC, Harn DA. A Schistosoma mansoni epitope recognized by a protective monoclonal antibody is identical to the stage-specific embryonic antigen 1. Proc Natl Acad Sci USA 1990;87:4159.

    Article  PubMed  CAS  Google Scholar 

  21. Eberl M, Langermans JA, Vervenne RA, et al. Antibodies to glycans dominate the host response to schistosome larvae and eggs: is their role protective or subversive? J Infect Dis 2001;183:1238.

    Article  PubMed  CAS  Google Scholar 

  22. Van Roon AM, Van de Vijver KK, Jacobs W, et al. Discrimination between the anti-monomeric and the anti-multimeric Lewis X response in murine schistosomiasis. Microbes Infect 2004;6:1125.

    Article  PubMed  CAS  Google Scholar 

  23. Robijn ML, Wuhrer M, Kornelis D, et al. Mapping fucosylated epitopes on glycoproteins and glycolipids of Schistosoma mansoni cercariae, adult worms and eggs. Parasitology 2005;130:67.

    Article  PubMed  CAS  Google Scholar 

  24. Remoortere A, Hokke CH, van Dam GJ, et al. Various stages of schistosoma express Lewis(x), LacdiNAc, GalNAcbeta1-4 (Fucalpha1-3G) lcNAc and GalNAc beta1-4(Fucalpha1-2Fucalpha1-3G) lcNAc carbohydrate epitopes: detection with monoclonal antibodies that are characterized by enzymatically synthesized neoglycoproteins. Glycobiology 2000;10:601.

    Article  PubMed  CAS  Google Scholar 

  25. Okano M, Satoskar AR, Nishizaki K, Abe M, Harn DA Jr. Induction of Th2 responses and IgE is largely due to carbohydrates functioning as adjuvants on Schistosoma mansoni egg antigens. J Immunol 1999;163:6712.

    PubMed  CAS  Google Scholar 

  26. Okano M, Satoskar AR, Nishizaki K, Harn DA Jr. Lacto-N-fucopentaose III found on Schistosoma mansoni egg antigens functions as adjuvant for proteins by inducing Th2-type response. J Immunol 2001;167:442.

    PubMed  CAS  Google Scholar 

  27. Palanivel V, Posey C, Horauf AM, et al. B-cell outgrowth and ligand-specific production of IL-10 correlate with Th2 dominance in certain parasitic diseases. Exp Parasitol 1996;84:168.

    Article  PubMed  CAS  Google Scholar 

  28. Velupillai P, Harn DA. Oligosaccharide-specific induction of interleukin 10 production by B220+ cells from schistosome-infected mice: a mechanism for regulation of CD4+ T-cell subsets. Proc Natl Acad Sci USA 1994;91:18.

    Article  PubMed  CAS  Google Scholar 

  29. Velupillai P, Secor WE, Horauf AM, Harn DA. B-1 cell (CD5+B220+) outgrowth in murine schistosomiasis is genetically restricted and is largely due to activation by polylactosamine sugars. J Immunol 1997;158:338.

    PubMed  CAS  Google Scholar 

  30. Levery SB, Weiss JB, Salyan ME, et al. Characterization of a series of novel fucosecontaining glycosphingolipid immunogens from eggs of Schistosoma mansoni. J Biol Chem 1992;267:5542.

    PubMed  CAS  Google Scholar 

  31. Nyame AK, Leppanen AM, Bogitsh BJ, Cummings RD. Antibody responses to the fucosylated LacdiNAc glycan antigen in Schistosoma mansoni-infected mice and expression of the glycan among schistosomes. Exp Parasitol 2000;96:202.

    Article  PubMed  CAS  Google Scholar 

  32. Van der Kleij D, Van Remoortere A, Schuitemaker JH, et al. Triggering of innate immune responses by schistosome egg glycolipids and their carbohydrate epitope GalNAc beta 1-4(Fuc alpha 1-2Fuc alpha 1-3G) lcNAc. J Infect Dis 2002;185:531.

    Article  PubMed  Google Scholar 

  33. Harn DA, Mitsuyama M, David JR. Schistosoma mansoni. Anti-egg monoclonal antibodies protect against cercarial challenge in vivo. J Exp Med 1984;159:1371.

    Article  PubMed  CAS  Google Scholar 

  34. Richter D, Incani RN, Harn DA. Lacto-N-fucopentaose III (Lewis x), a target of the antibody response in mice vaccinated with irradiated cercariae of Schistosoma mansoni. Infect Immun 1996;64:1826.

    PubMed  CAS  Google Scholar 

  35. Tawill S, Le Goff L, Ali F, Blaxter M, Allen JE. Both free-living and parasitic nematodes induce a characteristic Th2 response that is dependent on the presence of intact glycans. Infect Immun 2004;72:398.

    Article  PubMed  CAS  Google Scholar 

  36. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145.

    Article  PubMed  CAS  Google Scholar 

  37. Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996;17:138.

    Article  PubMed  CAS  Google Scholar 

  38. Barton GM, Medzhitov R. Control of adaptive immune responses by Toll-like receptors. Curr Opin Immunol 2002;14:380.

    Article  PubMed  CAS  Google Scholar 

  39. Shortman K, Wu L. Parentage and heritage of dendritic cells. Blood 2001;97:3325.

    Article  PubMed  CAS  Google Scholar 

  40. Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol 2001;1:135

    Article  PubMed  CAS  Google Scholar 

  41. Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767.

    Article  PubMed  CAS  Google Scholar 

  42. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245.

    Article  PubMed  CAS  Google Scholar 

  43. Lane PJ, Brocker T. Developmental regulation of dendritic cell function. Curr Opin Immunol 1999;11:308.

    Article  PubMed  CAS  Google Scholar 

  44. Moser M, Murphy KM. Dendritic cell regulation of TH1-TH2 development. Nat Immunol 2000;1:199.

    Article  PubMed  CAS  Google Scholar 

  45. Janeway CA Jr. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 1989;54Pt 1:1.

    PubMed  CAS  Google Scholar 

  46. Stahl PD, Ezekowitz RA. The mannose receptor is a pattern recognition receptor involved in host defense. Curr Opin Immunol 1998;10:50.

    Article  PubMed  CAS  Google Scholar 

  47. Hoyle GW, Hill RL. Molecular cloning and sequencing of a cDNA for a carbohydrate binding receptor unique to rat Kupffer cells. J Biol Chem 1988;263:7487.

    PubMed  CAS  Google Scholar 

  48. Geijtenbeek TB, Engering A, Van Kooyk Y. DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology. J Leukoc Biol 2002;71:921.

    PubMed  CAS  Google Scholar 

  49. Figdor CG, van Kooyk Y, Adema GJ. C-type lectin receptors on dendritic cells and Langerhans cells. Nat Rev Immunol 2002;2:77.

    Article  PubMed  CAS  Google Scholar 

  50. Shepherd VL, Konish MG, Stahl P. Dexamethasone increases expression of mannose receptors and decreases extracellular lysosomal enzyme accumulation in macrophages. J Biol Chem 1985;260:160.

    PubMed  CAS  Google Scholar 

  51. Reis e Sousa C. Dendritic cells as sensors of infection. Immunity 2001;14:495.

    Article  CAS  Google Scholar 

  52. Pulendran B, Kumar P, Cutler CW, et al. Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo. J Immunol 2001;167:5067.

    PubMed  CAS  Google Scholar 

  53. Pfenninger A, Karas M, Finke B, Stahl B, Sawatzki G. Mass spectrometric investigations of human milk oligosaccharides. Adv Exp Med Biol 2001;501:279.

    PubMed  CAS  Google Scholar 

  54. Erney R, Hilty M, Pickering L, Ruiz-Palacios G, Prieto P. Human milk oligosaccharides: a novel method provides insight into human genetics. Adv Exp Med Biol 2001;501:285.

    PubMed  CAS  Google Scholar 

  55. Kelder B, Erney R, Kopchick J, Cummings R, Prieto P. Glycoconjugates in human and transgenic animal milk. Adv Exp Med Biol 2001;501:269.

    PubMed  CAS  Google Scholar 

  56. DeBose-Boyd R, Nyame AK, Cummings RD. Schistosoma mansoni: characterization of an alpha 1-3 fucosyltransferase in adult parasites. Exp Parasitol 1996;82:1.

    Article  PubMed  CAS  Google Scholar 

  57. Srivatsan J, Smith DF, Cummings RD. Schistosoma mansoni synthesizes novel biantennary Asn-linked oligosaccharides containing terminal beta-linked N-acetylgalactosamine. Glycobiology 1992;2:445.

    Article  PubMed  CAS  Google Scholar 

  58. de Jong EC, Vieira PL, Kalinski P, et al. Microbial compounds selectively induce Th1 cell-promoting or Th2 cell-promoting dendritic cells in vitro with diverse th cell-polarizing signals. J Immunol 2002;168:1704.

    PubMed  Google Scholar 

  59. MacDonald AS, Straw AD, Bauman B, Pearce EJ. CD8-dendritic cell activation status plays an integral role in influencing Th2 response development. J Immunol 2001;167:1982.

    PubMed  CAS  Google Scholar 

  60. MacDonald AS, Straw AD, Dalton NM, Pearce EJ. Cutting edge: Th2 response induction by dendritic cells: a role for CD40. J Immunol 2002;168:537.

    PubMed  CAS  Google Scholar 

  61. Thomas PG, Carter MR, Atochina O, et al. Maturation of dendritic cell 2 phenotype by a helminth glycan uses a Toll-like receptor 4-dependent mechanism. J Immunol 2003;171:5837.

    PubMed  CAS  Google Scholar 

  62. Kaisho T, Hoshino K, Iwabe T, et al. Endotoxin can induce MyD88-deficient dendritic cells to support Th)(2 cell differentiation. Int Immunol 2002;14:695.

    Article  PubMed  CAS  Google Scholar 

  63. van Die I, van Vliet SJ, Nyame AK, et al. The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x. Glycobiology 2003;13:471.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Otolaryngology, Okayama University Medical School, Okayama, Japan

    Mitsuhiro Okano MD, PhD & Kazunori Nishizaki PhD

  2. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA

    Akram Da’dara PhD, Michele Carter MS & Donald A. Harn Jr. PhD

  3. Department of Immunology, St. Jude’s Children’s Research Hospital, Memphis, TN

    Paul Thomas PhD

Authors
  1. Mitsuhiro Okano MD, PhD
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  2. Kazunori Nishizaki PhD
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  3. Akram Da’dara PhD
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  4. Paul Thomas PhD
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  5. Michele Carter MS
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  6. Donald A. Harn Jr. PhD
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Editor information

Editors and Affiliations

  1. Division of Allergy, Immunology, and Transplantation National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD

    Charles J. Hackett PhD

  2. Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, MA

    Donald A. Harn Jr. MD

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© 2006 Humana Press Inc., Totowa, NJ

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Okano, M., Nishizaki, K., Da’dara, A., Thomas, P., Carter, M., Harn, D.A. (2006). The Immunomodulatory Glycan LNFPIII/Lewis X Functions As a Potent Adjuvant for Protein Antigens. In: Hackett, C.J., Harn, D.A. (eds) Vaccine Adjuvants. Infectious Disease. Humana Press. https://doi.org/10.1007/978-1-59259-970-7_9

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