title: Enhanced potency of plasmid DNA microparticle human immunodeficiency virus vaccines in rhesus macaques by using a priming-boosting regimen with recombinant proteins.
abstract: DNA vaccines have been used widely in experimental primate models of human immunodeficiency virus (HIV), but their effectiveness has been limited. In this study, we evaluated three technologies for increasing the potency of DNA vaccines in rhesus macaques. These included DNA encoding Sindbis virus RNA replicons (pSINCP), cationic poly(lactide-co-glycolide) (PLG) microparticles for DNA delivery, and recombinant protein boosting. The DNA-based pSINCP replicon vaccines encoding HIV Gag and Env were approximately equal in potency to human cytomegalovirus (CMV) promoter-driven conventional DNA vaccines (pCMV). The PLG microparticle DNA delivery system was particularly effective at enhancing antibody responses induced by both pCMV and pSINCP vaccines and had less effect on T cells. Recombinant Gag and Env protein boosting elicited rapid and strong recall responses, in some cases to levels exceeding those seen after DNA or DNA/PLG priming. Of note, Env protein boosting induced serum-neutralizing antibodies and increased frequencies of gamma interferon-producing CD4 T cells severalfold. Thus, PLG microparticles are an effective means of delivering DNA vaccines in nonhuman primates, as demonstrated for two different types of DNA vaccines encoding two different antigens, and are compatible for use with DNA prime-protein boost regimens.
authors.affiliation: Chiron Corporation, 4560 Horton St., Mail Stop 4.3, Emeryville, California 94608, USA. gillis_otten@chiron.com
authors.forename: Gillis R
authors.initials: GR
authors.lastname: Otten
authors.forename: Mary
authors.initials: M
authors.lastname: Schaefer
authors.forename: Barbara
authors.initials: B
authors.lastname: Doe
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Indresh
authors.initials: I
authors.lastname: Srivastava
authors.forename: Jan zur
authors.initials: Jz
authors.lastname: Megede
authors.forename: Jina
authors.initials: J
authors.lastname: Kazzaz
authors.forename: Ying
authors.initials: Y
authors.lastname: Lian
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.forename: Mildred
authors.initials: M
authors.lastname: Ugozzoli
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Mark
authors.initials: M
authors.lastname: Lewis
authors.forename: David A
authors.initials: DA
authors.lastname: Driver
authors.forename: Thomas
authors.initials: T
authors.lastname: Dubensky
authors.forename: John M
authors.initials: JM
authors.lastname: Polo
authors.forename: John
authors.initials: J
authors.lastname: Donnelly
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
authors.forename: Susan
authors.initials: S
authors.lastname: Barnett
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Ulmer
mesh_terms: D016915:AIDS Vaccines; D000818:Animals; D004279:DNA, Viral / Q000494:pharmacology*; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D010957:Plasmids / Q000235:genetics*; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA; D014764:Viral Proteins / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D004279:DNA, Viral; D015686:Gene Products, env; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014764:Viral Proteins