PMID: 18329757
Title: Enhancement of HIV DNA vaccine immunogenicity by the NKT cell ligand alpha galactosylceramide
Abstract: 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.
Date: 1970-08-21
Year: 2008
Journal: Vaccine
PMID Author: Huang Y, Chen A, Li X, Chen Z, Zhang W, Song Y, Gurner D, Gardiner D, Basu S, Ho DD, Tsuji M
Enhancement of HIV DNA vaccine immunogenicity by the NKT cell ligand, alpha-galactosylceramide. Vaccine 2008;26(15):1807-16 doi: 10.1016/j.vaccine.2008.02.002

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