alpha-Galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor

J Immunol. 2005 Sep 1;175(5):3309-17. doi: 10.4049/jimmunol.175.5.3309.


alpha-Galactosylceramide (alpha-GalCer) is a ligand of invariant Valpha14+ NKT cells and is presented by CD1d molecule on APC. NKT cells produce a large amount of Th1 and Th2 cytokines in response to alpha-GalCer-presented APC. In this study, we assessed whether alpha-GalCer could act as an effective nasal vaccine adjuvant for mucosal vaccine that would be capable of inducing systemic as well as mucosal immune responses. When alpha-GalCer was administered with OVA via the intranasal route to C57BL/6 and BALB/c mice, significant OVA-specific mucosal secretory IgA, systemic IgG, and CTL responses were induced with mixed Th1 and Th2 cytokine profiles seen in both strains of mice. Interestingly, as BALB/c mice were intranasally immunized with PR8 hemagglutinin Ag isolated from influenza virus A/PR/8/34 together with alpha-GalCer, significant protection was afforded against influenza viral infection. When alpha-GalCer was coimmunized with a replication-deficient live adenovirus to BALB/c mice, it significantly induced both humoral and cellular immune responses. In addition, intranasal administration of OVA with alpha-GalCer showed complete protection against EG7 tumor challenge in C57BL/6. The adjuvant effects induced by intranasal coadministration with alpha-GalCer were blocked in CD1d-/- mice, indicating that the immune responses were exclusively mediated by CD1d molecule on APC. Most interestingly, intranasally coadministered alpha-GalCer activated naive T cells and triggered them to differentiate into functional effector T cells when CFSE-labeled OT-1 cells were adoptively transferred into syngeneic mice. Overall, our results are the first to show that alpha-GalCer can act as a nasal vaccine adjuvant inducing protective immune responses against viral infections and tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Administration, Intranasal
  • Animals
  • Antigens, CD1 / physiology
  • Antigens, CD1d
  • Cancer Vaccines / administration & dosage*
  • Cytokines / biosynthesis
  • Defective Viruses / immunology
  • Female
  • Galactosylceramides / pharmacology*
  • Immunoglobulin A, Secretory / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Ovalbumin / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Viral Vaccines / administration & dosage*


  • Adjuvants, Immunologic
  • Antigens, CD1
  • Antigens, CD1d
  • Cancer Vaccines
  • Cytokines
  • Galactosylceramides
  • Immunoglobulin A, Secretory
  • Immunoglobulin G
  • Viral Vaccines
  • alpha-galactosylceramide
  • Ovalbumin