Mannosylated liposomes as antigen delivery vehicles for targeting to dendritic cells

Abstract

The immune stimulating ability of mannosylated liposomes containing FITC-ovalbumin as a model antigen and displaying either a branched tri-mannose or a mono-mannose ligand on the liposome surface was investigated in human monocyte-derived dendritic cells (MoDCs) and murine bone-marrow-derived dendritic cells (BMDCs). Uptake of liposomes, dendritic cell activation and proliferation of CD8(+) T cells from OT-I transgenic mice were determined by flow cytometry. Uptake of liposomes displaying the tri-mannose ligand was enhanced in human MoDCs compared with both non-mannosylated liposomes and liposomes displaying mono-mannose ligands. However, this increased uptake did not result in an increase in expression of CD80 or CD86 on the surface of the MoDCs. In contrast, neither tri-mannose- nor mono-mannose-containing liposomes were taken up by murine BMDCs to a greater extent than non-mannose-containing liposomes. The expression of CD86 and CD40 on the surface of BMDCs was not increased after exposure to mannosylated liposomes and BMDCs incubated with mannosylated liposomes were not able to stimulate proliferation of CD8(+) T cells to any greater extent than BMDCs incubated with non-mannosylated liposomes. These findings suggest that while mannose-containing ligands can enhance the uptake of antigen-containing liposomes by some dendritic cells, important differences in the affinity of carbohydrate-binding receptors for mannose-containing ligands do exist between species. In addition, the increase in uptake of antigen by dendritic cells using mannosylated liposomes does not necessarily result in enhanced dendritic cell activation.

Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesothelioma

“…2B, left and middle, arrows). CLIP has also been reported to target subsets of dendritic cells (26,37). Only a few dendritic cells are identified in explanted tumor spheroids (arrows) and these cells did not show CM-DiI red fluorescence (Fig.…”

Liposomal adjuvant development for leishmaniasis vaccines

“…Introduction of ligands or monoclonal antibodies like mannose, anti-DEC-205 Ab, anti-Clec9A Ab, or anti-DC-SIGN Ab for DC surface receptors improved the efficiency of targeted delivery of liposomes to DCs. [76][77][78] A list of important DC surface receptors which can be used as a target to strongly enhance cellular and humoral immune responses can be found in the literature. 79,80 A liposomal SLA formulation consisting of DPPC, cholesterol, and mannopentaose-dipalmitoylphosphatidylethanolamine (Man5-DPPE) was prepared to study its protective response in BALB/c mice against leishmaniasis.…”

Synthesis, Characterization and Immunological Evaluation of Self‐Adjuvanting Group A Streptococcal Vaccine Candidates Bearing Various Lipidic Adjuvanting Moieties

“…[21] Therefore, DC and macrophage uptake assays were performed according to the literature. [35][36] The vaccine candidates 1a-d were labeled with Dil (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) and incubated with DCs and macrophages, which were derived from mouse splenocytes. Following incubation with Dil labeled 1a-d, the cells were labelled with CD11c-A660 and F4/80-APC-Cy7 antibodies for DCs and macrophages, respectively, and their fluorescence was measured by flow cytometry.…”