Session 48Poster Presentations Vaccine Adjuvants Session Day and Time: Tuesday 1:30 - 3:30 pm Room: Hall D
396 Adjuvant Effects of an NKT Ligand, alpha-Galactosylceramide, on DNA Vaccination Y. Huang*1, Z. Chen1, W. Zhang1, Y. Song1, D. Gurner1, D. Gardiner1, A. Chen2, M. Tsuji1,2, D. D. Ho1 1Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY and 2New York Univ
Background: DNA vaccines show great promise as an alternative to conventional vaccination in numerous animal models; however, results from human trials suggest that their immunogenicity may be limited. Recently, the natural killer T-cell (NKT) ligand, alpha-galactosylceramide (alpha-GalCer), has been shown to have adjuvant effects by enhancing the protective immune response induced by malaria vaccines. We, therefore, undertook to test the adjuvant activity of alpha-GalCer on HIV-1 DNA vaccines in mice.
Methods: We vaccinated mice with several HIV-1 DNA vaccines encoding HIV-1 gag and env genes in the presence or absence of alpha-GalCer. Cell mediated immune responses (CMI) were assessed in splenocytes using an antigen-specific IFN-gamma ELISpot assay, and antibody responses to vaccine antigens were measured by ELISA.
Results: We found that co-administration of alpha-GalCer with suboptimal doses of DNA vaccines enhances CMI responses, including not only antigen-specific CD8+ T-cell responses (5- to 6-fold) but also CD4+ T-cell responses (~2-fold). The enhancement of CMI responses is antigen-independent and alpha-GalCer dose-dependent. When used as part of a DNA prime-DNA boost regimen, the adjuvant activity of alpha-GalCer is most profound when co-administered with DNA at the priming, but not the boosting phase. In a dose-sparing experiment, we show that the level of CMI responses in mice vaccinated with low-dose (5 µg) DNA in the presence of alpha-GalCer is equivalent to that of the mice vaccinated with 50 µg of DNA in the absence of alpha-GalCer. We further assessed the antibody response to viral antigens expressed by DNA vaccines, and show that the presence of alpha-GalCer during the priming phase enhances the antibody titer by 10-fold. The improved antibody response may result from higher antigen-specific CD4+ T-helper responses as measured by IL-4 ELISpot. Finally, results from CD1d and IFN-gamma receptor knockout mice demonstrate mechanistic dependence upon these molecules.
Conclusions: To our knowledge, this is the first time that alpha-GalCer has been shown to enhance the immunogenicity of DNA vaccines. Since both mice and humans share the CD1d molecule, this information may aid in designing more effective vaccines against HIV-1.
