Skip to main content

Advertisement

Log in

Mucosal adjuvant activity of oligomannose-coated liposomes for nasal immunization

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

In the present study, we investigated the effectiveness of liposomes coated with a neoglycolipid consisting of mannotriose and dipalmitoylphosphatidylcholine (Man3-DPPE) as an adjuvant for induction of mucosal immunity. Immunization of BALB/c mice with ovalbumin (OVA)-encapsulated Man3-DPPE-coated liposomes (oligomannose-coated liposomes; OMLs) by a nasal route produced high levels of OVA-specific IgG and IgA antibodies in serum of immunized mice 1 week after the last nasal immunization, whereas no significant serum antibody responses were observed in mice that received OVA in uncoated liposomes or OVA alone. Seven weeks after the last nasal immunization, nasal challenge with an excess amount of OVA in mice that had received OVA/OMLs led to an anamnestic response to the antigen that resulted in 5- to 10-fold increases of antigen-specific serum IgG and IgA antibodies. Only mice immunized nasally with OML/OVA secreted antigen-specific secretory IgA in nasal washes and produced interferon-gamma secreting cells in nasopharyngeal-associated lymphoreticular tissue. Taken together, these results show that nasal administration of OMLs induces mucosal and systemic immunity that are specific for the entrapped antigen in the liposomes. Thus, liposomes coated with synthetic neoglycolipids might be useful as adjuvants for induction of mucosal immunity.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Husband, A.J.: Novel vaccination strategies for the control of mucosal infection. Vaccine 11, 107–112 (1993)

    Article  CAS  PubMed  Google Scholar 

  2. Bowersock, T.L., Hogenesch, H., Suckow, M., Porter, R.E., Jackson, R., Park, H., Park, K.: Oral vaccination with alginate microsphere systems. J. Control. Release 39, 209–220 (1996)

    Article  CAS  Google Scholar 

  3. Kamiya, N., Asano, Y., Yoshino, J., Sasaki, K., Honma, Y., Kawase, H., Yokochi, T., Shiraki, K., Tsuji, T.: Long-term persistence of cellular immunity to Oka vaccine virus induced by pernasal co-administration with Escherichia coli enterotoxin in mice. Vaccine 19, 3131–3136 (2001)

    Article  CAS  PubMed  Google Scholar 

  4. Vajdy, M., Lycke, N.Y.: Cholera toxin adjuvant promotes long-term immunological memory in the gut mucosa to unrelated immunogens after oral immunization. Immunology 75, 488–492 (1992)

    CAS  PubMed  Google Scholar 

  5. Rappuoli, R., Pizza, M., Douce, G., Dougan, G.: Structure and mucosal adjuvanticity of cholera and Escherichia coli heat-labile enterotoxins. Immunol Today 20, 493–500 (1999)

    Article  CAS  PubMed  Google Scholar 

  6. Takahashi, I., Marinaro, M., Kiyono, H., Jackson, R.J., Nakagawa, I., Fujihashi, K., Hamada, S., Clements, J.D., Bost, K.L., McGhee, J.R.: Mechanisms for mucosal immunogenicity and adjuvancy of Escherichia coli labile enterotoxin. J. Infect. 173, 627–635 (1996)

    CAS  Google Scholar 

  7. Williams, N.A., Hirst, T.R., Nashar, T.O.: Immune modulation by the cholera-like enterotoxins: from adjuvant to therapeutic. Immunol Today 20, 95–101 (1999)

    Article  CAS  PubMed  Google Scholar 

  8. Krieg, A.M.: Immune effects and mechanisms of action of CpG motifs. Vaccine 19, 618–622 (2000)

    Article  CAS  PubMed  Google Scholar 

  9. McCluskie, M.J., Davis, H.L.: CpG DNA as mucosal adjuvant. Vaccine 18, 231–237 (1999)

    Article  CAS  PubMed  Google Scholar 

  10. Heikenwalder, M., Polymenidou, M., Junt, T., Sigurdson, C., Wagner, H., Akira, S., Zinkernagel, R., Aguzzi, A.: Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nat Med 10, 187–192 (2004)

    Article  CAS  PubMed  Google Scholar 

  11. Takagi, H., Furuya, N., Kojima, N.: Preferential production of IL-12 by peritoneal macrophages activated by liposomes prepared from neoglycolipids containing oligomannose residues. Cytokine 40, 241–250 (2007)

    Article  CAS  PubMed  Google Scholar 

  12. Kojima, N., Biao, L., Nakayama, T., Ishii, M., Ikehara, Y., Tsujimura, K.: Oligomannose-coated liposomes as a therapeutic antigen-delivery and an adjuvant vehicle for induction of in vivo tumor immunity. J. Control. Release 129, 26–32 (2008)

    Article  CAS  PubMed  Google Scholar 

  13. Fukasawa, M., Shimizu, Y., Shikata, K., Nakata, M., Sakakibara, R., Yamamoto, N., Hatanaka, M., Mizuochi, T.: Liposome oligomannose-coated with neoglycolipid, a new candidate for a safe adjuvant for induction of CD8+ cytotoxic T lymphocytes. FEBS Lett 441, 353–356 (1998)

    Article  CAS  PubMed  Google Scholar 

  14. Fujimura, Y., Akisada, T., Harada, T., Haruma, K.: Uptake of microparticles into the epithelium of human nasopharyngeal lymphoid tissue. Med. Mol. Morphol. 39, 181–186 (2006)

    Article  PubMed  Google Scholar 

  15. Bacon, A., Makin, J., Sizer, P.J., Jabbal-Gill, I., Hinchcliffe, M., Illum, L., Chatfield, S., Roerts, M.: Carbohydrate biopolymers enhance antibody responses to mucosally delivered vaccine antigens. Infect Immun 68, 5764–5770 (2000)

    Article  CAS  PubMed  Google Scholar 

  16. Stambas, J., Pietersz, G., McKenzie, I., Cheers, C.: Oxidised mannan as a novel adjuvant inducing mucosal IgA production. Vaccine 20, 1068–1078 (2002)

    Article  CAS  PubMed  Google Scholar 

  17. Shimizu, Y., Takagi, H., Nakayama, T., Yamakami, K., Tadakuma, T., Yokoyama, N., Kojima, N.: Intraperitoneal immunization with oligomannose-coated liposome-entrapped soluble leishmanial antigen induces antigen-specific T-helper type 1 immune response in BALB/c mice through uptake by peritoneal macrophages. Parasit. Immunol. 29, 229–239 (2007)

    Article  CAS  Google Scholar 

  18. Stevens, T.L., Bossie, A., Sanders, V.M., Fernandez-Botran, R., Coffman, R.L., Mosmann, T.R., Vitetta, E.S.: Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature 334, 255–258 (1988)

    Article  CAS  PubMed  Google Scholar 

  19. Wu, H.-Y., Russell, M.W.: Induction of mucosal and systemic immune responses by intranasal immunization using recombinant cholera toxin B subunit as an adjuvant. Vaccine 16, 286–292 (1997)

    Article  Google Scholar 

  20. Prabhala, R.H., Wira, C.R.: Cytokine regulation of the mucosal immune system: in vivo stimulation by interferon-gamma of secretory component and immunoglobulin A in uterine secretions and proliferation of lymphocytes from spleen. Endocrinology 129, 2915–2923 (1991)

    Article  CAS  PubMed  Google Scholar 

  21. Piskurich, J.F., France, J.A., Tamer, C.M., Willmer, C.A., Kaetzel, C.S., Kaetzel, D.M.: Interferon-gamma induces polymeric immunoglobulin receptor mRNA in human intestinal epithelial cells by a protein synthesis dependent mechanism. Mol Immunol 30, 413–421 (1993)

    Article  CAS  PubMed  Google Scholar 

  22. Yuki, Y., Kiyono, H.: New generation of mucosal adjuvants for the induction of protective immunity Rev. Med. Virol. 13, 293–310 (2003)

    Article  CAS  Google Scholar 

  23. Kunisawa, J., Nakanishi, T., Takahashi, I., Okudaira, A., Tsutsumi, Y., Katayama, K., Nakagawa, S., Kiyono, H., Mayumi, T.: Sendai virus fusion protein mediates simultaneous induction of MHC class I/II-dependent mucosal and systemic immune responses via the nasopharyngeal-associated lymphoreticular tissue immune system. J. Immunol. 167, 1406–1412 (2001)

    CAS  PubMed  Google Scholar 

  24. Harokopakis, E., Hajishengallis, G., Michalek, S.M.: Effectiveness of liposomes possessing surface-linked recombinant B subunit of cholera toxin as an oral antigen delivery system. Infect Immun 66, 4299–4304 (1998)

    CAS  PubMed  Google Scholar 

  25. Tana Watarai, S., Isogai, E., Oguma, K.: Induction of intestinal IgA and IgG antibodies preventing adhesion of verotoxin-producing Escherichia coli to Caco-2 cells by oral immunization with liposomes. Lett Appl Microbiol 36, 135–139 (2003)

    Article  Google Scholar 

  26. Joseph, A., Louria-Hayon, I., Plis-Finarov, A., Zeira, E., Zakay-Rones, Z., Raz, E., Hayashi, T., Takabayashi, K., Barenholz, Y., Kedar, E.: Liposomal immunostimulatory DNA sequence (ISS-ODN): an efficient parenteral and mucosal adjuvant for influenza and hepatitis B vaccines. Vaccine 20, 3342–3354 (2002)

    Article  CAS  PubMed  Google Scholar 

  27. Jain, S., Singh, P., Mishra, V., Vyas, S.P.: Mannosylated niosomes as adjuvant-carrier system for oral genetic immunization against hepatitis B. Immunol Lett 101, 41–49 (2005)

    Article  CAS  PubMed  Google Scholar 

  28. Ikehara, Y., Niwa, T., Biao, L., Kabata-Ikehara, S., Ohashi, N., Kobayashi, T., Shimizu, Y., Kojima, N., Nakanishi, H.: A carbohydrate recognition-based drug delivery and controlled release system using intraperitoneal macrophages as a cellular vehicle. Cancer Res 66, 8740–8748 (2006)

    Article  CAS  PubMed  Google Scholar 

  29. Ikehara, Y., Kojima, N.: Development of a novel oligomannose-coated liposome-based anticancer drug delivery system for intraperitoneal cancer. Curr opin mol ther 9, 53–61 (2007)

    CAS  PubMed  Google Scholar 

  30. Jakobsen, H., Schulz, D., Pizza, M., Rappuoli, R., Jónsdóttir, I.: Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections. Infect Immun 67, 5892–5897 (1999)

    CAS  PubMed  Google Scholar 

  31. Abraham, E., Shah, S.: Intranasal immunization with liposomes containing IL-2 enhances bacterial polysaccharide antigen-specific pulmonary secretory antibody response. J Immunol. 149, 3719–3726 (1992)

    CAS  PubMed  Google Scholar 

  32. Ninomiya, A., Ogasawara, K., Kajino, K., Takada, A., Kida, H.: Intranasal administration of a synthetic peptide vaccine encapsulated in liposome together with an anti-CD40 antibody induces protective immunity against influenza A virus in mice. Vaccine 20, 3123–3129 (2002)

    Article  CAS  PubMed  Google Scholar 

  33. Ikehara, Y., Shiuchi, N., Kabata-Ikehara, S., Nakanishi, H., Yokoyama, N., Takagi, H., Nagata, T., Koide, Y., Kuzushima, K., Takahashi, T., Tsujimura, K., Kojima, N.: Effective induction of anti-tumor immune responses with oligomannose-coated liposome targeting to intraperitoneal phagocytic cells. Cancer Lett 260, 137–145 (2008)

    Article  CAS  PubMed  Google Scholar 

  34. Owen, R.L., Pierce, N.F., Apple, R.T., Cray Jr., W.C.: M cell transport of Vibrio cholerae from the intestinal lumen into Peyer's patches: a mechanism for antigen sampling and for microbial transepithelial migration. Infect. Dis. 153, 1108–1118 (1986)

    CAS  Google Scholar 

  35. Robinson, M.J., Sancho, D., Slack, E.C., LeibundGut-Landmann, S., Reis e Sousa, C.: Myeloid C-type lectins in innate immunity. Nat. Immunol 7, 1258–1265 (2006)

    Article  CAS  PubMed  Google Scholar 

  36. Takagi, H., Numazaki, M., Kajiwara, T., Abe, Y., Ishii, M., Kato, C., Kojima, N.: Cooperation of specific ICAM-3 grabbing nonintegrin related 1 (SIGNR1) and complement receptor type 3 (CR3) in uptake of oligomannose-coated liposomes by macrophages. Glycobiology 19, 258–266 (2009)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Program for Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN), and in part by a Grant-in-Aid for Special Research from The Promotion and Mutual Aid Corporation for Private Schools of Japan.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Naoya Kojima.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ishii, M., Kojima, N. Mucosal adjuvant activity of oligomannose-coated liposomes for nasal immunization. Glycoconj J 27, 115–123 (2010). https://doi.org/10.1007/s10719-009-9263-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-009-9263-8

Keywords

Navigation