Mucosal adjuvant activity of oligomannose-coated liposomes for nasal immunization

Abstract

In the present study, we investigated the effectiveness of liposomes coated with a neoglycolipid consisting of mannotriose and dipalmitoylphosphatidylcholine (Man3-DPPE) as an adjuvant for induction of mucosal immunity. Immunization of BALB/c mice with ovalbumin (OVA)-encapsulated Man3-DPPE-coated liposomes (oligomannose-coated liposomes; OMLs) by a nasal route produced high levels of OVA-specific IgG and IgA antibodies in serum of immunized mice 1 week after the last nasal immunization, whereas no significant serum antibody responses were observed in mice that received OVA in uncoated liposomes or OVA alone. Seven weeks after the last nasal immunization, nasal challenge with an excess amount of OVA in mice that had received OVA/OMLs led to an anamnestic response to the antigen that resulted in 5- to 10-fold increases of antigen-specific serum IgG and IgA antibodies. Only mice immunized nasally with OML/OVA secreted antigen-specific secretory IgA in nasal washes and produced interferon-gamma secreting cells in nasopharyngeal-associated lymphoreticular tissue. Taken together, these results show that nasal administration of OMLs induces mucosal and systemic immunity that are specific for the entrapped antigen in the liposomes. Thus, liposomes coated with synthetic neoglycolipids might be useful as adjuvants for induction of mucosal immunity.

Targeting with oligomannose-coated liposomes promotes maturation and splenic trafficking of dendritic cells in the peritoneal cavity

“…DCs are also the main source of IL-12 [16]. Both intraperitoneal and subcutaneous or intranasal administrations of OMLs induce strong antigen-specific Th1 immune responses and protect against subsequent protozoan infections, tumor inoculation, and allergic reactions when specific antigens are entrapped within the OMLs [17][18][19][20]. This suggests that OMLs can activate APCs such as DCs that are present in local tissues, but it is unclear if DCs take up OMLs and if the adjuvant effects of OMLs result from modulation of DC function and maturation.…”

Oligomannose-Coated Liposome as a Novel Adjuvant for the Induction of Cellular Immune Responses to Control Disease Status

“…This inhibitory effect might occur through a shift from a Th2 immune response to an allergen-specific Th1 immune response, since Cry j 1-specific IgG1, which is mediated by Th2 cells, was significantly reduced, whereas Cry j 1-specific IgG2a, which is produced by Th1 cells, was increased in sera from OML-based vaccinated mice. Recently, it was demonstrated that intranasal administration of OML-based vaccines could induce both mucosal and systemic immune responses and suppress the development of allergic diarrhea induced by oral OVA administration [67, 68]. Therefore, OML-encased allergens may serve as immunotherapeutic agents to control allergic diseases including food allergies.…”

‘Smart‘ non-viral Delivery Systems for Targeted Delivery of RNAi to the Lungs

“…Using a ligand targeting strategy for liposome drug delivery has many advantages including increasing target specificity and avoiding the need for cationic lipids to trigger intracellular delivery. Ligands such as antibodies for example anti-CC531 antibodies [111], polysaccharides such as O-stearyl amylopectin (O-SAP), glycolipids such as Man3-DPPE and mannosylated cholesterol (Mann-C4-Chol) [112][113][114], peptides such as Arg-Gly-Asp (RGD) [115] and glycoproteins can be incorporated into liposome formulations for macrophage targeting. Hasida and colleagues have evaluated mannosylated liposomes targeting macrophages and DCs for the delivery of anti-inflammatory agents such as dexamethasone palmitate (dex) [116] and NFκB decoy and anti-cancer agents including CpG oligonucleotides and DNA [117].…”