Skip to main content
SpringerLink
Log in

Vaccines and Immunomodulation

  • Chapter
  • First Online:
Biomedical Applications of Peptide-, Glyco- and Glycopeptide Dendrimers, and Analogous Dendrimeric Structures

Abstract

Dendrimers, due to their unique chemical and biological properties, are considered to be highly suitable tools for regulation of immunity. They are endowed with unique capacity to expose artificial multivalent carbohydrate, glycoprotein or peptide antigens as highly defined three dimensional structures. A number of experimental vaccines has been developed against both infectious diseases and cancer. Notably, dendrimers can also be designed to be preferentially targeted to antigen-presenting cells and to activate them. As nucleic acid carriers, they can be utilized as carriers in DNA vaccines.

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

  1. Allen, J., Harris, C., Danishefsky, S.: Pursuit of optimal carbohydrate-based anticancer vaccines: Preparation of a multiantigenic unimolecular glycopeptide containing the Tn, MBr1, and Lewisy antigens. J. Am. Chem. Soc. 123(9), 1890–1897 (2001)

    Article  PubMed  CAS  Google Scholar 

  2. Barata, T.S., Teo, I., Brocchini, S., Zloh, M., Shaunak, S.: Partially glycosylated dendrimers block MD-2 and prevent TLR4-MD-2-LPS complex mediated cytokine responses. PLoS Comput. Biol. 7(6), e1002095 (2011)

    Article  PubMed  CAS  Google Scholar 

  3. Bolhassani, A., Safaiyan, S., Rafati, S.: Improvement of different vaccine delivery systems for cancer therapy. Mol. Cancer 10(1), Art. No. 3 (2011)

    Google Scholar 

  4. Brocke, C., Kunz, H.: Synthesis of tumor-associated glycopeptide antigens. Bioorg. Med. Chem. 10(10), 3085–3112 (2002)

    Article  PubMed  CAS  Google Scholar 

  5. Buskas, T., Thompson, P., Boons, G.J.: Immunotherapy for cancer: synthetic carbohydrate-based vaccines. Chem. Commun. (36), 5335–5349 (2009)

    Article  Google Scholar 

  6. Chabre, Y., Roy, R.: Design and creativity in synthesis of multivalent neoglycoconjugates. Adv. Carbohydr. Chem. Biochem. 63, 165–393 (2010)

    Article  PubMed  CAS  Google Scholar 

  7. Cheng, Y., Zhao, L., Li, Y., Xu, T.: Design of biocompatible dendrimers for cancer diagnosis and therapy: Current status and future perspectives. Chem. Soc. Rev. 40(5), 2673–2703 (2011)

    Article  PubMed  CAS  Google Scholar 

  8. Cruz, L.J., Iglesias, E., Aguilar, J.C., Gonzalez, L.J., Reyes, O., Albericio, F., Andreu, D.: A comparative study of different presentation strategies for an HIV peptide immunogen. Bioconjug. Chem. 15(1), 112–120 (2004)

    Article  PubMed  CAS  Google Scholar 

  9. Cubillos, C., de la Torre, B.G., Jakab, A., Clementi, G., Borras, E., Barcena, J., Andreu, D., Sobrino, F., Blanco, E.: Enhanced mucosal immunoglobulin A response and solid protection against foot-and-mouth disease virus challenge induced by a novel dendrimeric peptide. J. Virol. 82(14), 7223–7230 (2008)

    Article  PubMed  CAS  Google Scholar 

  10. Daftarian, P., Kaifer, A.E., Li, W., Blomberg, B.B., Frasca, D., Roth, F., Chowdhury, R., Berg, E.A., Fishman, J.B., Al Sayegh, H.A., Blackwelder, P., Inverardi, L., Perez, V.L., Lemmon, V., Serafini, P.: Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells. Cancer Res. 71(24), 7452–7462 (2011)

    Article  PubMed  CAS  Google Scholar 

  11. Danishefsky, S., Allen, J.: From the laboratory to the clinic: A retrospective on fully synthetic carbohydrate-based anticancer vaccines. Angew. Chem. Int. Ed. 39(5), 836–863 (2000)

    Article  CAS  Google Scholar 

  12. Dudkin, V., Orlova, M., Geng, X., Mandal, M., Olson, W., Danishefsky, S.: Toward fully synthetic carbohydrate-based HIV antigen design: on the critical role of bivalency. J. Am. Chem. Soc. 126(31), 9560–9562 (2004)

    Article  PubMed  CAS  Google Scholar 

  13. Dziadek, S., Hobel, A., Schmitt, E., Kunz, H.: A fully synthetic vaccine consisting of a tumor-associated glycopeptide antigen and a T-cell epitope for the induction of a highly specific humoral immune response. Angew. Chem. Int. Ed. 44(46), 7630–7635 (2005)

    Article  CAS  Google Scholar 

  14. Dziadek, S., Kunz, H.: Synthesis of tumor-associated glycopeptide antigens for the development of tumor-selective vaccines. Chem. Rec. 3(6), 308–321 (2004)

    Article  PubMed  CAS  Google Scholar 

  15. Fruchon, S., Poupot, M., Martinet, L., Turrin, C.O., Majoral, J.P., Fournie, J.J., Caminade, A.M., Poupot, R.: Anti-inflammatory and immunosuppressive activation of human monocytes by a bioactive dendrimer. J. Leukocyte Biol. 85(3), 553–562 (2009)

    Article  PubMed  CAS  Google Scholar 

  16. Galonic, D., Gin, D.: Chemical glycosylation in the synthesis of glycoconjugate antitumour vaccines. Nature 446(7139), 1000–1007 (2007)

    Article  PubMed  CAS  Google Scholar 

  17. Geng, X., Dudkin, V.Y., Mandal, M., Danishefsky, S.J.: In pursuit of carbohydrate-based HIV vaccines, part 2: The total synthesis of high-mannose-type gp120 fragmentsevaluation of strategies directed to maximal convergence. Angew. Chem. Int. Ed. 43(19), 2562–2565 (2004)

    Article  CAS  Google Scholar 

  18. Gilewski, T., Ragupathi, G., Bhuta, S., Williams, L., Musselli, C., Zhang, X.F., Bencsath, K., Panageas, K., Chin, J., Hudis, C., Norton, L., Houghton, A., Livingston, P., Danishefsky, S.: Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: A phase I trial. Proc. Natl. Acad. Sci. USA 98(6), 3270–3275 (2001)

    Article  PubMed  CAS  Google Scholar 

  19. Gilewski, T., Ragupathi, G., Dickler, M., Powell, S., Bhuta, S., Panageas, K., Koganty, R., Chin-Eng, J., Hudis, C., Norton, L., Houghton, A., Livingston, P.: Immunization of high-risk breast cancer patients with clustered STn-KLH conjugate plus the immunologic adjuvant QS-21. Clin. Cancer Res. 13(10), 2977–2985 (2007)

    Article  PubMed  CAS  Google Scholar 

  20. Hakomori, S.I.: Tumor-associated carbohydrate antigens defining tumor malignancy: Basis for development of anti-cancer vaccines. Adv. Exp. Med. Biol. 491, 369–402 (2001)

    Article  PubMed  CAS  Google Scholar 

  21. Hang, H., Bertozzi, C.: The chemistry and biology of mucin-type O-linked glycosylation. Bioorg. Med. Chem. 13(17), 5021–5034 (2005)

    Article  PubMed  CAS  Google Scholar 

  22. Heegaard, P., Boas, U., Sorensen, N.: Dendrimers for vaccine and immunostimulatory uses. A review. Bioconjug. Chem. 21(3), 405–418 (2010)

    Article  CAS  Google Scholar 

  23. Heimburg-Molinaro, J., Lum, M., Vijay, G., Jain, M., Almogren, A., Rittenhouse-Olson, K.: Cancer vaccines and carbohydrate epitopes. Vaccine 29(48), 8802–8826 (2011)

    Article  PubMed  CAS  Google Scholar 

  24. Hevey, R., Ling, C.C.: Recent advances in developing synthetic carbohydrate-based vaccines for cancer immunotherapies. Future Med. Chem. 4(4), 545–584 (2012)

    Article  PubMed  CAS  Google Scholar 

  25. Holemann, A., Seeberger, P.: Carbohydrate diversity: Synthesis of glycoconjugates and complex carbohydrates. Curr. Opin. Biotechnol. 15(6), 615–622 (2004)

    Article  PubMed  Google Scholar 

  26. Hsu, C.H., Hung, S.C., Wu, C.Y., Wong, C.H.: Toward automated oligosaccharide synthesis. Angew. Chem. Int. Ed. 50(50), 11872–11923 (2011)

    Article  CAS  Google Scholar 

  27. Joyce, J.G., Krauss, I.J., Song, H.C., Opalka, D.W., Grimm, K.M., Nahas, D.D., Esser, M.T., Hrin, R., Feng, M., Dudkin, V.Y., Chastain, M., Shiver, J.W., Danishefsky, S.J.: An oligosaccharide-based HIV-1 2G12 mimotope vaccine induces carbohydrate-specific antibodies that fail to neutralize HIV-1 virions. Proc. Natl. Acad. Sci. USA 105(41), 15684–15689 (2008)

    Article  PubMed  CAS  Google Scholar 

  28. Kabaker, K., Shell, K., Kaufman, H.L.: Vaccines for colorectal cancer and renal cell carcinoma. Cancer J. 17(5), 283–293 (2011)

    Article  PubMed  CAS  Google Scholar 

  29. Keding, S., Danishefsky, S.: Synthetic carbohydrate-based vaccines. In: Carbohydrate-Based Drug Discovery, vol. 1, pp. 381–406. Wiley-VCH, Weinheim (2003)

    Google Scholar 

  30. Keil, S., Kaiser, A., Syed, F., Kunz, H.: Dendrimers of vaccines consisting of tumor-associated glycopeptide antigens and T cell epitope peptides. Synthesis (8), 1355–1369 (2009)

    Google Scholar 

  31. Koeller, K., Wong, C.H.: Synthesis of complex carbohydrates and glycoconjugates: enzyme-based and programmable one-pot strategies. Chem. Rev. 100(12), 4465–4493 (2000)

    Article  PubMed  CAS  Google Scholar 

  32. Krug, L., Ragupathi, G., Hood, C., Kris, M., Miller, V., Allen, J., Keding, S., Danishefsky, S., Gomez, J., Tyson, L., Pizzo, B., Baez, V., Livingston, P.: Vaccination of patients with small-cell lung cancer with synthetic fucosyl GM-1 conjugated to keyhole limpet hemocyanin. Clin. Cancer Res. 10(18 I), 6094–6100 (2004)

    Google Scholar 

  33. Kunz, H.: Synthetic glycopeptides for the development of tumour-selective vaccines. J. Pept. Sci. 9(9), 563–573 (2003)

    Article  PubMed  CAS  Google Scholar 

  34. Lepenies, B., Seeberger, P.H.: The promise of glycomics, glycan arrays and carbohydrate-based vaccines. Immunopharmacol Immunotoxicol. 32(2), 196–207 (2010)

    Article  PubMed  CAS  Google Scholar 

  35. Li, H., Wang, L.X.: Design and synthesis of a template-assembled oligomannose cluster as an epitope mimic for human HIV-neutralizing antibody 2G12. Org. Biomol. Chem. 2, 483–488 (2004)

    Article  PubMed  CAS  Google Scholar 

  36. Liakatos, A., Kunz, H.: Synthetic glycopeptides for the development of cancer vaccines. Curr. Opin. Mol. Ther. 9(1), 35–44 (2007)

    PubMed  CAS  Google Scholar 

  37. Lisowska, E.: The role of glycosylation in protein antigenic properties. Cell Mol. Life Sci. 59(3), 445–455 (2002)

    Article  PubMed  CAS  Google Scholar 

  38. Mandal, M., Dudkin, V.Y., Geng, X., Danishefsky, S.J.: In pursuit of carbohydrate-based HIV vaccines, part 1: The total synthesis of hybrid-type gp120 fragments. Angew. Chem. Int. Ed. 43(19), 2557–2561 (2004)

    Article  CAS  Google Scholar 

  39. Morelli, L., Poletti, L., Lay, L.: Carbohydrates and immunology: synthetic oligosaccharide antigens for vaccine formulation. Eur. J. Org. Chem. (29), 5723–5777 (2011)

    Article  Google Scholar 

  40. Nakada, H., Inoue, M., Numata, Y., Tanaka, N., Funakoshi, I., Fukui, S., Mellors, A., Yamashina, I.: Epitopic structure of Tn glycophorin A for an anti-Tn antibody (MLS128). Proc. Natl. Acad. Sci. USA 90(6), 2495–2499 (1993)

    Article  PubMed  CAS  Google Scholar 

  41. Niederhafner, P., Reinis, M., Sebestik, J., Jezek, J.: Glycopeptide dendrimers, Part III - a review: Use of glycopeptide dendrimers in immunotherapy and diagnosis of cancer and viral diseases. J. Pept. Sci. 14(5), 556–587 (2008)

    CAS  Google Scholar 

  42. Ouerfelli, O., Warren, J., Wilson, R., Danishefsky, S.: Synthetic carbohydrate-based antitumor vaccines: Challenges and opportunities. Expert Rev. Vaccines 4(5), 677–685 (2005)

    Article  PubMed  CAS  Google Scholar 

  43. Ragupathi, G., Gathuru, J., Livingston, P.: Antibody inducing polyvalent cancer vaccines. Cancer Treat. Res. 123, 157–180 (2005)

    Article  PubMed  CAS  Google Scholar 

  44. Sebestik, J., Niederhafner, P., Jezek, J.: Peptide and glycopeptide dendrimers and analogous dendrimeric structures and their biomedical applications. Amino Acids 40(2), 301–370 (2011)

    Article  PubMed  CAS  Google Scholar 

  45. Seitz, O.: Glycopeptide synthesis and the effects of glycosylation on protein structure and activity. ChemBioChem 1(4), 214–246 (2000)

    Article  PubMed  CAS  Google Scholar 

  46. Shaunak, S., Thomas, S., Gianasi, E., Godwin, A., Jones, E., Teo, I., Mireskandari, K., Luthert, P., Duncan, R., Patterson, S., Khaw, P., Brocchini, S.: Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation. Natl. Biotechnol. 22(8), 977–984 (2004)

    Article  CAS  Google Scholar 

  47. Sheng, K.C., Kalkanidis, M., Pouniotis, D.S., Esparon, S., Tang, C.K., Apostolopoulos, V., Pietersz, G.A.: Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo. Eur. J. Immunol. 38(2), 424–436 (2008)

    Google Scholar 

  48. Shiao, T.C., Roy, R.: Glycodendrimers as functional antigens and antitumor vaccines. New J. Chem. 36(2), 324–339 (2012)

    Article  CAS  Google Scholar 

  49. Slovin, S., Keding, S., Ragupathi, G.: Carbohydrate vaccines as immunotherapy for cancer. Immunol. Cell Biol. 83(4), 418–428 (2005)

    Article  PubMed  CAS  Google Scholar 

  50. Slovin, S., Ragupathi, G., Adluri, S., Ungers, G., Terry, K., Kim, S., Spassova, M., Bornmann, W., Fazzari, M., Dantis, L., Olkiewicz, K., Lloyd, K., Livingston, P., Danishefsky, S., Scher, H.: Carbohydrate vaccines in cancer: Immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man. Proc. Natl. Acad. Sci. USA 96(10), 5710–5715 (1999)

    Article  PubMed  CAS  Google Scholar 

  51. Slovin, S., Ragupathi, G., Musselli, C., Olkiewicz, K., Verbel, D., Kuduk, S., Schwarz, J., Sames, D., Danishefsky, S., Livingston, P., Scher, H.: Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate cancer: Clinical trial results with α-N-acetylgalactosamine-O- serine/threonine conjugate vaccine. J. Clin. Oncol. 21(23), 4292–4298 (2003)

    Article  PubMed  CAS  Google Scholar 

  52. Tarradas, J., Monso, M., Munoz, M., Rosell, R., Fraile, L., Frias, M.T., Domingo, M., Andreu, D., Sobrino, F., Ganges, L.: Partial protection against classical swine fever virus elicited by dendrimeric vaccine-candidate peptides in domestic pigs. Vaccine 29(26), 4422–4429 (2011)

    Article  PubMed  CAS  Google Scholar 

  53. Tekade, R., Kumar, P., Jain, N.: Dendrimers in oncology: An expanding horizon. Chem. Rev. 109(1), 49–87 (2009)

    Article  PubMed  CAS  Google Scholar 

  54. Trkola, A., Purtscher, M., Muster, T., Ballaun, C., Buchacher, A., Sullivan, N., Srinivasan, K., Sodroski, J., Moore, J.P., Katinger, H.: Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J. Virol. 70(2), 1100–1108 (1996)

    PubMed  CAS  Google Scholar 

  55. Verminnen, K., Beeckman, D.S.A., Sanders, N.N., De Smedt, S., Vanrompay, D.C.G.: Vaccination of turkeys against Chlamydophila psittaci through optimised DNA formulation and administration. Vaccine 28(18), 3095–3105 (2010)

    Article  PubMed  CAS  Google Scholar 

  56. Vichier-Guerre, S., Lo-Man, R., BenMohamed, L., Driaud, E., Kovats, S., Leclerc, C., Bay, S.: Induction of carbohydrate-specific antibodies in HLA-DR transgenic mice by a synthetic glycopeptide: A potential anti cancer vaccine for human use. J. Pept. Res. 62(3), 117–124 (2003)

    Article  PubMed  CAS  Google Scholar 

  57. Wang, J., Li, H., Zou, G., Wang, L.X.: Novel template-assembled oligosaccharide clusters as epitope mimics for HIV-neutralizing antibody 2G12. Design, synthesis, and antibody binding study. Org. Biomol. Chem. 5(10), 1529–1540 (2007)

    Google Scholar 

  58. Westerlind, U., Kunz, H.: Synthetic vaccines from tumor-associated glycopeptide antigens. Chimia 65(1–2), 30–34 (2011)

    Article  PubMed  CAS  Google Scholar 

  59. Wolinsky, J., Grinstaff, M.: Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv. Drug Deliv. Rev. 60(9), 1037–1055 (2008)

    Article  PubMed  CAS  Google Scholar 

  60. Zaman, M., Skwarczynski, M., Malcolm, J.M., Urbani, C.N., Jia, Z., Batzloff, M.R., Good, M.F., Monteiro, M.J., Toth, I.: Self-adjuvanting polyacrylic nanoparticulate delivery system for group A streptococcus (GAS) vaccine. Nanomed 7(2), 168–173 (2011)

    Article  CAS  Google Scholar 

  61. Zhu, J., Warren, J., Danishefsky, S.: Synthetic carbohydrate-based anticancer vaccines: the memorial Sloan-Kettering experience. Expert Rev. Vaccines 8(10), 1399–1413 (2009)

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Spectroscopy, Institute of Organic Chemistry and Biochemistry, AS CR, vvi, Prague, Czech Republic

    Jaroslav Šebestík

  2. Institute of Molecular Genetics AS CR, vvi, Prague, Czech Republic

    Milan Reiniš

  3. Laboratory of Glycoconjugates, Institute of Organic Chemistry and Biochemistry, AS CR, vvi, Prague, Czech Republic

    Jan Ježek

Authors
  1. Jaroslav Šebestík
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Milan Reiniš
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan Ježek
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Wien

About this chapter

Cite this chapter

Šebestík, J., Reiniš, M., Ježek, J. (2012). Vaccines and Immunomodulation. In: Biomedical Applications of Peptide-, Glyco- and Glycopeptide Dendrimers, and Analogous Dendrimeric Structures. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1206-9_22

Download citation

Publish with us

Policies and ethics

Search

Navigation