Enhanced Potency of Plasmid DNA Microparticle Human Immunodeficiency Virus Vaccines in Rhesus Macaques by Using a Priming-Boosting Regimen with Recombinant Proteins
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Published:2005-07
Issue:13
Volume:79
Page:8189-8200
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ISSN:0022-538X
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Container-title:Journal of Virology
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language:en
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Short-container-title:J Virol
Author:
Otten Gillis R.1, Schaefer Mary1, Doe Barbara1, Liu Hong1, Srivastava Indresh1, zur Megede Jan1, Kazzaz Jina1, Lian Ying1, Singh Manmohan1, Ugozzoli Mildred1, Montefiori David2, Lewis Mark3, Driver David A.1, Dubensky Thomas1, Polo John M.1, Donnelly John1, O'Hagan Derek T.1, Barnett Susan1, Ulmer Jeffrey B.1
Affiliation:
1. Chiron Corporation, Emeryville, California 2. Duke University Medical Center, Durham, North Carolina 3. Southern Research Institute, Frederick, Maryland
Abstract
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.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
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