Antigen delivery systems are important for inducing and modifying immune responses. A key to development of vaccines is the ability to deliver antigens to antigen-presenting cells (APCs) more efficiently and to induce subsequent activation of T cell-mediated immunity. Thus, strategies that target APCs and modulate APC functions in vivo have significant implications for vaccine design. We have demonstrated that oligomannose-coated liposomes (OMLs), which consist of DPPC, cholesterol, Man3-DPPE at a molar ratio of 10:10:1, can induce strong cellular immunity. In this review, we discuss OMLs as novel antigen-delivery vehicles that also have a strong adjuvant effect on induction of Th1 immune responses and CTLs specific for the encased antigen. This property of OMLs is due to their ability to assist specific cellular uptake in vivo and to promote subsequent APC maturation, presentation of antigens on APCs, preferential secretion of IL-12 from APCs, and migration of APCs into lymphoid tissues from peripheral tissues. Administration of an OML-based vaccine can eliminate an established tumor, inhibit elevation of the serum level of IgE against an allergen, and prevent progression of some protozoan infections in mouse models. In addition, OMLs with an encased antigen are able to induce antigen-specific CTLs in PBMCs obtained from patients. These feasibility studies of OML-based vaccines have revealed their potential for clinical use in vaccination for diseases in which CTLs and/or Th1 cells act as effector cells.
Glycosylation is the most frequent modification of proteins and is important for many ligand-receptor interactions. We have attempted to demonstrate the biosynthetic pathway and the function of O-mannosyl glycan since 1997 when the O-mannosyl glycan structure was identified. In this study, we have identified and characterized glycosyltransferases, POMT1, POMT2 and POMGnT1. Mutations in POMT1, POMT2 or POMGnT1 can lead to a congenital muscular dystrophy with abnormal neuronal migration. Our findings indicate that O-mannosyl glycan plays an important role in muscle and brain development. This review briefly outlines the biosynthetic mechanism of O-mannosyl glycan in mammals.
Metalloglycoclusters, part of the glycocluster family, are an attractive group of functional molecules comprising a metal complex decorated with carbohydrate moieties. Metalloglycoclusters possessing both organic and inorganic components show unique fluorescent, electrochemical and magnetic properties absent in glycoclusters. Despite their unique and diverse functionalities, investigations of metalloglycoclusters have just begun to make progress with the development of applications and methodologies related to biological fields. In this minireview, we describe the potential use of metalloglycoclusters as functional molecules particularly in the light of recent reports (including our reports) pertaining to their application for analyzing carbohydrate binding properties and for imaging living cells.
Sulfated polysaccharides are related to recognition and many biological activities in an organism. The action mechanism has become apparent by means of nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR) apparatus. In this minireview, we describe the recent synthesis, biological activity, and relationship between structure and biological activity of polysaccharides.