Induction of specific adaptive immune responses by immunization with newly designed artificial glycosphingolipids

We previously found that artificial glycosphingolipids (artGSLs) containing very-long-chain fatty acids behave as strong immunogens in mice and promote the production of antibodies recognizing the oligosaccharide portion of artGSLs as the epitope. Here, we report that the oligosaccharide structure of artGSLs influences these immunogenic properties. We evaluated the antibody-inducing activity of artGSLs with different oligosaccharide structures in mice and found strong IgG-inducing activity only with an artGSL containing a core-fucosylated tetraoligosaccharide (Manβ1,4GlcNAcβ1,4[Fucα1,6]GlcNAc). To characterize the immunogenic properties of this artGSL, we analyzed various derivatives and found that the non-reducing terminal mannose structure was critical for the antibody-inducing activity. These artGSLs also exhibited IgG-inducing activity dependent on co-administration of lipid A adjuvant, but no cytokine-inducing activity similar to α-galactosylceramide was detected. Furthermore, repetitive immunization with the artGSL promoted the production of antibodies against a core-fucosylated α-fetoprotein isoform (AFP-L3) known as a hepatocellular carcinoma-specific antigen. These results indicate that the newly designed artGSLs specifically induce adaptive immune responses and promote antibody production by B cells, which can be utilized to develop anti-glycoconjugate antibodies and cancer vaccines targeting tumor-associated carbohydrate antigens.