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ABSTRACT: A plasmid DNA vaccine containing a fusion gene consisting of an HIV-1 subtype C gag and a modified subtype C pol was compared to a mixture of gag plus pol or gag plus HIV env plasmids. Plasmid DNA was delivered by intramuscular injection followed by electroporation in vivo. Two vaccinations were sufficient to induce high levels of Gag- and Pol-specific CD4 and CD8 T cells in peripheral blood. The gag-pol fusion plasmid was as immunogenic as the plasmid mixtures. Thus, DNA vaccination by intramuscular electroporation was an effective means for inducing high levels of Gag- and Pol-specific T cells, and a single gag-pol fusion DNA vaccine was sufficient for eliciting immune responses against both antigens.
Vaccine 06/2006; 24(21):4503-9. · 3.77 Impact Factor
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Gillis R Otten, Mary Schaefer,
Barbara Doe,
Hong Liu,
Indresh Srivastava,
Jan zur Megede,
Jina Kazzaz,
Ying Lian,
Manmohan Singh,
Mildred Ugozzoli,
David Montefiori,
Mark Lewis,
David A Driver,
Thomas Dubensky,
John M Polo,
John Donnelly,
Derek T O'Hagan,
Susan Barnett,
Jeffrey B Ulmer
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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.
Journal of Virology 08/2005; 79(13):8189-200. · 5.40 Impact Factor
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Gillis Otten, Mary Schaefer,
Barbara Doe,
Hong Liu,
Indresh Srivastava,
Jan zur Megede,
Derek O'Hagan,
John Donnelly,
Georg Widera,
Dietmar Rabussay,
Mark G Lewis,
Susan Barnett,
Jeffrey B Ulmer
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ABSTRACT: The potency of an HIV DNA vaccine was enhanced in rhesus macaques by in vivo electroporation, as judged by increased onset, magnitude and duration of antibody and cell-mediated immune responses against both components of a combination Gag and Env vaccine. These data demonstrate the utility of the electroporation technology for use in large animals.
Vaccine 07/2004; 22(19):2489-93. · 3.77 Impact Factor
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Gillis Otten, Mary Schaefer,
Catherine Greer,
Maria Calderon-Cacia,
Doris Coit,
Jina Kazzaz,
Angelica Medina-Selby,
Mark Selby,
Manmohan Singh,
Mildred Ugozzoli,
Jan zur Megede,
Susan W Barnett,
Derek O'Hagan,
John Donnelly,
Jeffrey Ulmer
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ABSTRACT: Several vaccine technologies were evaluated for their abilities to induce anti-human immunodeficiency virus Gag immune responses in rhesus macaques. While no vaccine alone was able to induce broad and strong immune responses, these were achieved by priming with Gag DNA and boosting with Gag protein adsorbed to polylactide coglycolide microparticles. This regimen elicited strong antibodies, helper T cells, and cytotoxic T lymphocytes and thus holds promise as an effective vaccination scheme.
Journal of Virology 06/2003; 77(10):6087-92. · 5.40 Impact Factor
