A novel synthetic bipartite carrier protein for developing glycotope-based vaccines

Abstract

Development of successful vaccines against glycotopes remains a major challenge. In the current studies, we have successfully developed a novel carrier protein for glycotopes based on the concept of antigen clustering and specific stimulation of T helper cells to mount strong antibody response to glycotopes. The bipartite carrier protein consists of a tandem repeat of a cysteine-rich peptide for docking of clustered glycotopes to effectively activate B cells and an Fc domain for antigen delivery to antigen presenting cells (APCs). To demonstrate its utility, we conjugated the tumor-specific monosaccharide antigen Tn to this novel carrier protein and successfully developed a Tn vaccine against cancer in animal models. The Tn vaccine effectively elicited high-titer IgG1 antibodies against Tn in immunized mice, and effectively suppressed the development of prostate cancer in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice. Our results suggest that this novel bipartite carrier protein could be effectively used for developing anti-glycotope vaccines such as the anticancer Tn vaccine.