NY-ESO-1-antiMR antibody bound to the MR on DCs and NY-ESO-1-anti-DEC-205 on DCs, leading to stimulation of CD4+ and CD8+ T cells from peripheral blood mononuclear cells of cancer patients . In contrast, nonantibody targeted NY-ESO-1 proteins only activated CD4+ T cells. Thus, targeting either the MR or DEC205 on DCs is a promising vaccination strategy to induce
strong cellular immune responses. In order to retain the characteristics of mannose rich carbohydrates and target the MR on DCs, antigens were expressed in yeast. Several recombinant ovalbumin (OVA) proteins were generated in Pichia Pastoris Inhibitors,research,lifescience,medical which naturally mannosylated OVA . Mannosylated OVA induced enhanced Paclitaxel in vitro antigen-specific CD4+ T-cell proliferation compared to non-mannosylated OVA, and, uptake was primarily due to mannose-specific C-type lectin receptors (MR and DC-SIGN) . Further, stronger CTL responses and IFN-gamma, IL-2, IL-4, IL-5 cytokines were induced after vaccination Inhibitors,research,lifescience,medical in mice . These studies demonstrate that yeast derived mannosylation of antigens enhances immunogenicity. Therapeutic strategies using tumor-specific immunoglobulin (idiotype, Id) for lymphomas are promising. Id proteins are usually produced via tumor-myeloma hybridomas Inhibitors,research,lifescience,medical or recombinant methods in mammalian, bacteria, or insect cells. Using insect cells, the Id produced contain mannose residues which have enhanced immunostimulatory
properties (activation of DCs, CD8+ T-cell stimulation, and eradication of lymphomas), compared to Id proteins made in mammalian cells . However, anti-lymphoma antibodies generated by Id insect cell compared to mammalian cells were similar. Thus, insect derived antigens are far more immunostimulatory compared to mammalian Inhibitors,research,lifescience,medical derived antigens, primarily due to the expression of mannose which binds to the
MR. Humans with suppressed T cells have high prevalence of Cryptococcosis. Soluble Cryptococcus neoformans mannoproteins (MP) are promising vaccine candidates due to their ability to induces delayed-type hypersensitivity and Th1 cytokines. MP binds to the MR Inhibitors,research,lifescience,medical and results in CD4+ T-cell stimulation and induce protective responses against C. neoformans and Candida albicans. The uptake of MP by DCs can be inhibited either by competitive blockade of the MR or by removal of carbohydrate residues critical for recognition . Further, MPs increased the expression of CD40, CD83, CD86, MHC class I and II cell surface enough moleules, and IL-12 leading to the maturation and activation of DCs . It was clear that the mannose groups on MP provided the immunogenicity of cryptococcal MP and this finding supports vaccination strategies that target the MR. It is clear that antigen mannosylation is an effective approach to potentiate antigen immunogenicity, due to the enhanced antigen uptake and presentation by DCs and macrophages. 2.2. Group 2 C-Type Lectin Receptors: Asialoglycoprotein Receptor Family 2.