A key to development of vaccines is the ability to deliver antigens to APCs and to activate APCs more efficiently for induction of subsequent adaptive immunity. Thus, strategies that target APCs and modulate APC functions have significant implications for vaccine design. It is becoming clear that lectin receptors expressed on APCs are particularly important PRRs for capture of pathogens, and thus the carbohydrates recognized by lectin receptors can be used as targeting signals to APCs. We have demonstrated that oligomannose-coated liposomes (OMLs) can induce strong cellular immunity. In this study, we summarize OMLs as novel antigen-delivery vehicles that have a strong adjuvant effect on induction of cellular immunity and describe an application of OMLs to ex vivo activation of mononuclear phagocytes.
OMLs have an ability to assist specific uptake into mononuclear phagocytes and to promote subsequent cell maturation, effective presentation of antigens, preferential secretion of IL-12, and migration of the cells 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 as well as human models. In addition, the inflammatory monocytes in murine and human PBMC could ingest OMLs preferentially in vitro and differentiate into mature APCs in response to in vitro uptake of OMLs. Human MoDCs also preferentially ingested OMLs, and in response to OML uptake, expression of CD86 and HLA-DR was upregulated with significant production of IL-12, suggesting that OML-stimulated MoDCs showed a preferable fully matured status.
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 and for ex vivo generation of antigen-presented mature MoDCs without any additional proinflammatory mediators.