title: Enhancing efficacy of HIV gag DNA vaccine by local delivery of GM-CSF in murine and macaque models.
abstract: Controlled release of granulocyte-macrophage colony-stimulating factor (GM-CSF) protein by albumin-heparin microparticles administered via intramuscular vaccination in conjunction with HIV DNA vaccines stimulated HIV Gag-specific immune responses. In the murine model, Gag-specific cytotoxic T lymphocyte (CTL) and T helper (Th) responses were significantly enhanced by administration of murine GM-CSF microparticles. This effect was comparable to a GM-CSF encoded plasmid. In three of four rhesus monkeys, enhancement of Gag-specific antibody (Ab), Th, and CTL responses was observed 1 month after the first immunization with coadministration of human GM-CSF microparticles and HIV Gag plasmid. The second, third, and fourth booster immunizations, however, did not increase the Gag-specific immune responses. Subsequent application of Gag protein in complete Freund's adjuvant (CFA) significantly enhanced Ab and Th, but not CTL. However, Gag-specific CTL response was triggered by cytokine and Gag p55-encapsulated microparticles in all animals. The strategy of priming immune responses by coadministration of cytokine microparticles and DNA vaccines, followed by boosting with cytokine and antigen protein-encapsulated microparticles, may prove effective in improving an HIV DNA vaccine design.
authors.affiliation: Department of Pharmacology and Molecular Sciences, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Ruijiang
authors.initials: R
authors.lastname: Song
authors.forename: Shuqin
authors.initials: S
authors.lastname: Liu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
mesh_terms: D000418:Albumins / Q000493:pharmacokinetics / Q000648:ultrastructure; D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D015683:Gene Products, gag / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology*; D006678:HIV; D006493:Heparin / Q000493:pharmacokinetics / Q000648:ultrastructure; D006801:Humans; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000276:immunology; D010957:Plasmids; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology
chemical_list: D000418:Albumins; D015683:Gene Products, gag; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006493:Heparin