Liposomal delivery of antigen to human dendritic cells.
This study investigated whether formulation of antigen in mannosylated liposomes enhanced uptake and activation of dendritic cells (DC) and increased the ability of DC to induce primed T cell proliferation compared to formulation of antigen in unmodified liposomes or in solution. Immature human DC were generated from peripheral blood monocytes cultured with GM-CSF and IL-4. Uptake of antigen by DC and the degree of expression of the cell surface markers MHC class II, CD80, CD86 and the DC maturation marker CD83, was investigated by flow cytometry following incubation with liposomes or solution containing FITC-conjugated antigen. Exposure to liposomes containing FITC-ovalbumin resulted in enhanced expression of cell surface markers when compared to exposure to antigen in solution. Expression was highest following exposure to mannosylated liposomes. Mannosylated liposomes containing tetanus toxoid (TT) stimulated primed T cell proliferation more effectively than TT-neutral liposomes or TT-solution. This work suggests that mannosylated liposomes provide a versatile delivery vehicle for initiating enhanced immune responses to encapsulated peptide or protein vaccines.
Copland
Melissa J
MJ
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Baird
Margaret A
MA
Rades
Thomas
T
McKenzie
Judith L
JL
Becker
Bernd
B
Reck
Folkert
F
Tyler
Peter C
PC
Davies
Nigel M
NM
D017951:Antigen Presentation; D000941:Antigens / Q000008:administration & dosage*; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012996:Solutions; D013601:T-Lymphocytes / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage; D000097802:CD83 Antigen
D000941:Antigens; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016650:Fluorescein-5-isothiocyanate; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D008081:Liposomes; D008562:Membrane Glycoproteins; D010047:Ovalbumin; D012996:Solutions; D013745:Tetanus Toxoid; D000097802:CD83 Antigen; C497964:CD86 protein, human