Enhancement of HIV DNA vaccine immunogenicity by the NKT cell ligand, alpha-galactosylceramide.
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.
Huang
Yaoxing
Y
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
Chen
Alex
A
Li
Xiangming
X
Chen
Zhiwei
Z
Zhang
Wenyong
W
Song
Yang
Y
Gurner
Deborah
D
Gardiner
David
D
Basu
Sankha
S
Ho
David D
DD
Tsuji
Moriya
M
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018949:Antigens, CD1 / Q000235:genetics; D055610:Antigens, CD1d; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage*; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000172:deficiency; D019444:Vaccines, DNA / Q000276:immunology*; D000096743:Interferon gamma Receptor
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; D017471:Receptors, Interferon; D019444:Vaccines, DNA; D000096743:Interferon gamma Receptor; C526877:CD1D protein, human; C493154:alpha-galactosylceramide