The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection

Jeffrey M. Jacobson, Lu Zheng, Cara C. Wilson, Pablo Tebas, Roy M. Matining, Michael A. Egan, John Eldridge, Alan L. Landay, David B. Clifford, Anne F. Luetkemeyer, Jennifer Tiu, Ana L. Martinez, Jennifer Janik, Teresa A. Spitz, John Hural, Juliana McElrath, Nicole Frahm

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background: Therapeutic vaccination is being studied in eradication and "functional cure" strategies for HIV-1. The Profectus Biosciences multiantigen (MAG) HIV-1 DNA vaccine encodes HIV-1 Gag/Pol, Nef/Tat/Vif, and Envelope, and interleukin-12 (IL-12) and is delivered by electroporation combined with intramuscular injection (IM-EP). Methods: Sixty-two HIV-1-infected patients on antiretroviral therapy (plasma HIV-1 RNA levels ≤200 copies/mL; CD4 + T-cell counts ≥500 cells/mm 3) were randomly allocated 5:1 to receive vaccine or placebo. At weeks 0, 4, and 12, 4 consecutive cohorts received 3000 g HIV MAG pDNA with 0, 50, 250, or 1000 g of IL-12 pDNA by IM-EP. A fifth cohort received HIV MAG pDNA and 1000 g of IL-12 pDNA by standard IM injection. Results: CD4 + T cells expressing IL-2 in response to Gag and Pol and interferon-γ responses to Gag, Pol, and Env increased from baseline to week 14 in the low-dose (50-g) IL-12 arm vs. placebo (P < 0.05; intracellular cytokine staining). The total increase in the IL-2-expressing CD4 + T-cell responses to any antigen was also higher in the low-dose IL-12 arm vs. placebo (P 0.04). Cytokine responses by CD8 T cells to HIV antigens were not increased in any vaccine arm relative to placebo. Conclusions: HIV-1 MAG/low-dose IL-12 DNA vaccine delivered by IM-EP augmented CD4 + but not CD8 + T-cell responses to multiple HIV-1 antigens.

Original languageEnglish
Pages (from-to)163-171
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume71
Issue number2
DOIs
StatePublished - Feb 1 2016

Keywords

  • DNA vaccine
  • HIV
  • electroporation
  • interleukin-12
  • therapeutic vaccination

Fingerprint

Dive into the research topics of 'The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection'. Together they form a unique fingerprint.

Cite this