title: Mechanisms of increased immunogenicity for DNA-based vaccines adsorbed onto cationic microparticles.
abstract: Investigation into the mechanism of action of vaccine adjuvants provides opportunities to define basic immune principles underlying the induction of strong immune responses and insights useful for the rational development of subunit vaccines. A novel HIV vaccine composed of plasmid DNA-encoding p55 gag formulated with poly-lactide-co-glycolide microparticles (PLG) and cetyl trimethyl ammonium bromide (CTAB) elicits both serum antibody titers and cytotoxic lymphocyte activity in mice at doses two orders of magnitude lower than those required for comparable response to plasmid DNA in saline. Using this model, we demonstrated the increase in potency requires the DNA to be complexed to the PLG-CTAB microparticles. Furthermore, the PLG-CTAB-DNA formulation increased the persistence of DNA at the injection site, recruited mononuclear phagocytes to the site of injection, and activated a population of antigen presenting cells. Intramuscular immunization with the PLG-CTAB-DNA complex induced antigen expression at both the injection site and the draining lymph node. These findings demonstrate that the PLG-CTAB-DNA formulation exhibits multiple mechanisms of immunopotentiation.
authors.affiliation: Department of Anatomy and Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA, USA. kimberly_denis-mize@chiron.com
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Denis-Mize
authors.forename: Marc
authors.initials: M
authors.lastname: Dupuis
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.forename: Carolyn
authors.initials: C
authors.lastname: Woo
authors.forename: Mildred
authors.initials: M
authors.lastname: Ugozzoli
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
authors.forename: John J
authors.initials: JJ
authors.lastname: Donnelly
authors.forename: Gary
authors.initials: G
authors.lastname: Ott
authors.forename: Donald M
authors.initials: DM
authors.lastname: McDonald
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000493:pharmacokinetics; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D000956:Antigens, Viral / Q000276:immunology; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008863:Microspheres; D011098:Polyglactin 910 / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019444:Vaccines, DNA / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000493:pharmacokinetics
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000890:Anti-Infective Agents; D000956:Antigens, Viral; D002593:Cetrimonium Compounds; D004279:DNA, Viral; D015683:Gene Products, gag; D019444:Vaccines, DNA; D011098:Polyglactin 910; D000077286:Cetrimonium