title: Liposome/DNA complexes coated with biodegradable PLA improve immune responses to plasmid encoding hepatitis B surface antigen.
abstract: We hypothesized that the addition of polymer to the surface of liposome/DNA complexes may potentially enhance in vivo delivery of plasmid DNA to antigen-presenting cells and thereby facilitate enhanced immune responses to encoded protein. BALB/c mice were immunized subcutaneously or intramuscularly three times with a total of 50 microg of the plasmid pRc/CMV-HBs(S) (ayw subtype) encoding for the hepatitis B surface antigen. We measured transgene-specific total immunoglobulin G (IgG), IgG2a, IgG2b and IgG1 antibody responses as well as splenocyte and T-cell proliferation and cytokine production upon re-stimulation following immunization. Modification of lipid/DNA complexes by the polymer precipitation method used here for the addition of poly(d,l-lactic acid) was found to be consistently and significantly more effective than either unmodified liposomal DNA or naked DNA in eliciting transgene-specific immune responses to plasmid-encoded antigen when administered by the subcutaneous route. In addition, the polymer-modified formulations delivered by this route were more effective than naked DNA delivered by the intramuscular route in inducing antibody responses (n=5, P<0.03). Our observations provide 'proof of principle' for the use of these multicomponent formulations, which offer potential for manipulation and increased transfection efficiency in vivo for the purposes of genetic immunization.
authors.affiliation: Centre for Drug Delivery Research, School of Pharmacy, University of London, UK.
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Bramwell
authors.forename: Jim E
authors.initials: JE
authors.lastname: Eyles
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Somavarapu
authors.forename: H Oya
authors.initials: HO
authors.lastname: Alpar
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004279:DNA, Viral / Q000008:administration & dosage*; D005260:Female; D018014:Gene Transfer Techniques; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000096:biosynthesis; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019076:Transgenes / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D008081:Liposomes; D011108:Polymers