8th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 4 - 8, 2001

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:51 (abstract no. 27)

G. Otten¹, M. Chen, B. Doe, J. Kazzaz, Y. Lian, H. Liu, L. Leung, G. Ott, J. Polo, M. Shaefer, M. Selby, M. Singh, Y. Sun, M. Ugozzoli, J. Zur Megede, M. Lewis, N. Miller, G. Widera, S. Barnett, J. Donnelly, D. O'Hagan, and J. Ulmer
¹Chiron Corp., Emeryville, CA; Southern Res. Inst., Frederick, MD; NIAID, NIH, Bethesda, MD; and Genetronics, San Diego, CA.

BACKGROUND: Plasmid DNA has several features that makes it attractive as a component of an HIV vaccine. However, clinical results suggest that the modest immunogenicity of plasmid DNA may limit its protective efficacy against HIV. We have developed and tested in rhesus macaques three distinct delivery technologies designed to overcome barriers that limit plasmid DNA immunogenicity. These enhancement methods include electric current-mediated electroporation to increase transfection efficiency in vivo, adsorption of plasmid DNA onto cationic poly(lactide-co- glycolide) (PLG) microparticles, and formulation of plasmid DNA with a cationic emulsion based on the adjuvant, MF59.

METHODS: Using plasmids containing codon-modified HIV p55^gag and gp140^env sequences, these delivery technologies were compared to intramuscular injection of plasmid DNA in saline (naked DNA).

RESULTS: All three technologies increased plasmid immunogenicity, with serum IgG ELISA titers and CD4 T helper lymphoproliferative responses that appeared more quickly and reached higher levels than those obtained in rhesus immunized with naked DNA. In addition, flow cytometric analysis of intracellular IFN-γ and TNF-α production demonstrated increased numbers of antigen-specific CD4 T cells in the peripheral blood of rhesus vaccinated by electroporation or with PLG microparticles. Antibodies capable of neutralizing HIV were seen after enhanced plasmid DNA immunization. HIV-specific CTL activity was observed in rhesus macaques vaccinated by electroporation, DNA/PLG, or naked DNA; however, CTL were almost undetectable after vaccination with DNA/MF59. These findings were corroborated by intracellular cytokine analysis.

CONCLUSION: Our results suggest that these plasmid delivery technologies may serve as important components of an effective HIV vaccine.

2001-02-04
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Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.