title: Immunostimulatory lipid implants containing Quil-A and DC-cholesterol.
abstract: Biocompatible lipid implants which promote the sustained release of antigen have potential as novel vaccine delivery systems for subunit antigen as they may reduce or remove the requirement for multiple administrations. Of particular interest are sustained release systems that release antigen incorporated into particles. Previous work has demonstrated that lipid implants prepared from phosphatidylcholine, cholesterol, the adjuvant Quil-A, and ovalbumin as the model antigen could stimulate an immune response equivalent to that induced by a prime and boost with a comparable injectable vaccine. However, entrapment of antigen into particles released from the implant was low. Therefore the aim of this study was to firstly determine if the inclusion of a cationic derivative of cholesterol, DC-cholesterol, into the implants increased antigen entrapment and immunogenicity, and secondly, if a cationic implant could induce at least a comparable immune response as compared to a prime and boost with an injectable vaccine. The inclusion of DC-cholesterol had only a minor effect on antigen entrapment into particles released from the implants and the implants did not stimulate cellular responses as effectively as the comparable injectable vaccine or the unmodified implant containing Quil-A and cholesterol, although the vaccine did induce stronger responses than either soluble protein alone, or protein co-delivered in alum.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Julia
authors.initials: J
authors.lastname: Myschik
authors.forename: Warren T
authors.initials: WT
authors.lastname: McBurney
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Sarah
authors.initials: S
authors.lastname: Hook
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry; D004339:Drug Compounding; D004343:Drug Implants; D007111:Immunity, Cellular; D007267:Injections; D007700:Kinetics; D008081:Liposomes; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D010713:Phosphatidylcholines / Q000737:chemistry; D062605:Quillaja Saponins; D012503:Saponins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D012995:Solubility; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000906:Antibodies; D004343:Drug Implants; D008081:Liposomes; D010713:Phosphatidylcholines; D062605:Quillaja Saponins; D012503:Saponins; D014612:Vaccines; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; C041524:aluminum sulfate; C046386:Quil A; D010047:Ovalbumin; D002784:Cholesterol