title: Modulation of cellular immune response against hepatitis C virus nonstructural protein 3 by cationic liposome encapsulated DNA immunization.
abstract: A vaccine strategy directed to increase Th1 cellular immune responses, particularly to hepatitis C virus (HCV) nonstructural protein 3 (NS3), has considerable potential to overcome the infection with HCV. DNA vaccination can induce both humoral and cellular immune responses, but it became apparent that the cellular uptake of naked DNA injected into muscle was not very efficient, as much of the DNA is degraded by interstitial nucleases before it reaches the nucleus for transcription. In this paper, cationic liposomes composed of different cationic lipids, such as dimethyl-dioctadecylammonium bromide (DDAB), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), or 1,2-dioleoyl-sn-glycerol-3-ethylphosphocholine (DOEPC), were used to improve DNA immunization in mice, and their efficiencies were compared. It was found that cationic liposome-mediated DNA immunization induced stronger HCV NS3-specific immune responses than immunization with naked DNA alone. Cationic liposomes composed of DDAB and equimolar of a neutral lipid, egg yolk phosphatidylcholine (EPC), induced the strongest antigen-specific Th1 type immune responses among the cationic liposome investigated, whereas the liposomes composed of 2 cationic lipids, DDAB and DOEPC, induced an antigen-specific Th2 type immune response. All cationic liposomes used in this study triggered high-level, nonspecific IL-12 production in mice, a feature important for the development of maximum Th1 immune responses. In conclusion, the cationic liposome-mediated gene delivery is a viable HCV vaccine strategy that should be further tested in the chimpanzee model.
authors.affiliation: Department of Transfusion Medicine, Warren G. Magnuson Clinical, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Xuanmao
authors.initials: X
authors.lastname: Jiao
authors.forename: Richard Y-H
authors.initials: RY
authors.lastname: Wang
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Feng
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Alter
authors.forename: James Wai-Kuo
authors.initials: JW
authors.lastname: Shih
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002214:Capsules; D002412:Cations; D002460:Cell Line; D005229:Fatty Acids, Monounsaturated; D018014:Gene Transfer Techniques; D007114:Immunization / Q000379:methods*; D018664:Interleukin-12 / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism*; D010957:Plasmids; D000644:Quaternary Ammonium Compounds; D018417:Th1 Cells / Q000276:immunology*; D014162:Transfection; D019444:Vaccines, DNA / Q000627:therapeutic use*; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D002214:Capsules; D002412:Cations; D005229:Fatty Acids, Monounsaturated; D018664:Interleukin-12; D008081:Liposomes; D010713:Phosphatidylcholines; D000644:Quaternary Ammonium Compounds; D019444:Vaccines, DNA; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C046112:didodecyldimethylammonium; C017251:1,2-oleoylphosphatidylcholine; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane