Sensitized liposomes as an antigen delivery system for the stimulation of mucosal immunity.
This study was designed to exploit the ability of Peyer's patch M cells to recognize antigen-antibody complexes in the targeted delivery of a model antigen for the induction of mucosal immunity. Sensitized liposomes consisted of an entrapped model antigen, ovalbumin (OVA), and coated with unrelated antigen-antibody complexes. Sensitized liposomes were administered intrajejunally to mice either with or without monophosphoryl lipid A (MLA). Humoral immune responses were monitored in saliva, feces, serum, and bile. Mice which received sensitized liposomes showed up to 4-fold amounts of specific IgA in saliva, feces, and bile compared to controls. Transient increases in anti-OVA IgA and IgG were observed in serum. Formulations including MLA generated positive anti-OVA IgG responses in both serum and bile. In separate experiments, cell proliferation studies were performed with Peyer's patch lymphocytes harvested from mice immunized with OVA in either standard or sensitized liposomes. Lymphocytes from test mice receiving only sensitized liposomes proliferated in the presence of OVA, but not an unrelated antigen. Taken together, these results support the potential application of antigen-antibody complexes in the stimulation of mucosal immune responses and that MLA may play an important role in overcoming OVA tolerogenicity.
Velez
C N
CN
Division of Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill 27599, USA.
Tonkonogy
S L
SL
Lichtman
S N
SN
Cho
M J
MJ
D000285:Administration, Rectal; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D001646:Bile / Q000276:immunology; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D004337:Drug Carriers; D005243:Feces / Q000737:chemistry; D005293:Ferritins / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009596:Nitrophenols / Q000737:chemistry / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology; D012463:Saliva / Q000276:immunology
D000941:Antigens; D004337:Drug Carriers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008081:Liposomes; D009596:Nitrophenols; D010047:Ovalbumin; D005293:Ferritins; D002772:Cholera Toxin