title: Enhancement of a human immunodeficiency virus env DNA vaccine using a novel polycationic nanoparticle formulation.
abstract: In an effort to develop a more effective DNA immunization strategy for HIV, we synthesized an HIV-2 env DNA vaccine and delivered it in a novel polycationic adjuvant formulation that forms nanoparticles in solution and enhances protein expression. The polycationic adjuvant contained imidazole moieties to facilitate endosomal escape. Nanoparticles containing the DNA vaccine plasmid were formed by electrostatic condensation with the polycationic adjuvant. We hypothesized that this formulation would improve immune responses to the gp140 env gene from HIV-2(UC2) by increasing the level of expressed antigen. We found that the nanoparticles were superior at inducing high levels of systemic antibody responses compared to naked DNA when delivered by the intradermal route in BALB/c mice. In addition, the nanoparticles induced higher levels of IgM, IgG, and IgA antibodies. These results suggest that nanoparticles may be an important adjuvant formulation to improve the effectiveness of genetic immunization and rationalize its use in the evaluation of vaccine candidates in non-human primate models for AIDS.
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, CA 94143-1270, USA. christopher.locher@maxygen.com
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Locher
authors.forename: David
authors.initials: D
authors.lastname: Putnam
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Witt
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Ashlock
authors.forename: Jay A
authors.initials: JA
authors.lastname: Levy
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015498:HIV-2 / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D036103:Nanotechnology; D011073:Polyamines / Q000737:chemistry* / Q000276:immunology*; D000071228:Polyelectrolytes; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D011073:Polyamines; D000071228:Polyelectrolytes; D011498:Protein Precursors; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C066315:gp140 envelope protein, Human immunodeficiency virus 2