Research Labs: Moriya Tsuji, M.D., Ph.D.
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Identification of novel synthetic analogues of alpha-GalCer, as an immuno-enhancing molecule for vaccines against HIV and malaria

            Although many attempts have been made to develop HIV and malaria vaccines, they have been unsuccessful to date.  The main reason for this failure is that the vaccines have not been immunologically strong, that is immunogenic enough to prevent the infection and/or to prolong anti-HIV/malaria immunity.  Therefore, it is essential to develop a compound that can significantly enhance the immunogenicity of HIV/malaria vaccines.  Our previous studies have demonstrated that a CD1d molecule-binding, natural killer T (NKT) cell ligand, alpha-galactosylceramide (alpha-GalCer), can enhance the immunogenicity of vaccines against HIV and malaria in a mouse model.  Most recently, we have discovered that modification of alpha-GalCer can results in compounds with stronger biological activity (NKT cell stimulating activity) than alpha-GalCer.  Therefore, our main goal is to determine whether some of the alpha-GalCer analogues could display a far superior immuno-enhancing activity, thereby greatly improving the efficacy of vaccines against HIV and malaria.