Enhanced potency of plasmid DNA microparticle human immunodeficiency virus vaccines in rhesus macaques by using a priming-boosting regimen with recombinant proteins.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Otten, GR; Schaefer, M; Doe, B; Liu, H; Srivastava, I; Megede, JZ; Kazzaz, J; Lian, Y; Singh, M; Ugozzoli, M; Montefiori, D; Lewis, M; Driver, DA; Dubensky, T; Polo, JM; Donnelly, J; O'Hagan, DT; Barnett, S; Ulmer, JB

Published Date

  • July 2005

Published In

Volume / Issue

  • 79 / 13

Start / End Page

  • 8189 - 8200

PubMed ID

  • 15956564

Pubmed Central ID

  • 15956564

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/JVI.79.13.8189-8200.2005

Language

  • eng

Conference Location

  • United States