Enhancement of HIV DNA vaccine immunogenicity by the NKT cell ligand, alpha-galactosylceramide

Vaccine. 2008 Mar 28;26(15):1807-16. doi: 10.1016/j.vaccine.2008.02.002. Epub 2008 Feb 20.


A number of studies have shown that the natural killer T cell (NKT) ligand alpha-galactosylceramide (alpha-GalCer) serves as an adjuvant for various vaccines, including viral vaccines, parasite vaccines and protein vaccines. In this report, we investigated the adjuvant activity of alpha-GalCer on HIV-1 DNA vaccines in mice. This is a first study to show that alpha-GalCer can enhance the immunogenicity of DNA vaccines, since co-administration of alpha-GalCer with suboptimal doses of DNA vaccines greatly enhanced antigen-specific CD4+ T-cell and CD8+ T-cell responses. Differently from other vaccines, alpha-GalCer was also able to enhance HIV-specific antibody response 10-fold. It is of practical importance to find out that, in a DNA prime-DNA boost regimen, the adjuvant activity of alpha-GalCer was most profound when co-administered at the priming, but not at the boosting phase. In a dose-sparing experiment, we found that the level of cell-mediated immune responses in mice vaccinated with 5 microg of DNA in the presence of alpha-GalCer was equivalent to that of mice vaccinated with 50 microg of DNA in the absence of alpha-GalCer. Finally, results from CD1d and interferon-gamma receptor knockout mice confirm our previous data and determine the mechanistic dependence upon these molecules. These results illustrate that alpha-GalCer enhances the immunogenicity of DNA vaccines in a mechanism-based fashion. Since both mice and humans share the CD1d molecule, this information may aid in designing more effective DNA vaccines and vaccine adjuvants against HIV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antibodies, Viral / blood
  • Antigens, CD1 / genetics
  • Antigens, CD1d
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Galactosylceramides / administration & dosage*
  • HIV Infections / prevention & control
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Immunization, Secondary / methods
  • Interferon gamma Receptor
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Receptors, Interferon / deficiency
  • Vaccines, DNA / immunology*


  • AIDS Vaccines
  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Antigens, CD1
  • Antigens, CD1d
  • CD1D protein, human
  • Galactosylceramides
  • Receptors, Interferon
  • Vaccines, DNA
  • alpha-galactosylceramide