title: The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection.
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 μg HIV MAG pDNA with 0, 50, 250, or 1000 μg of IL-12 pDNA by IM-EP. A fifth cohort received HIV MAG pDNA and 1000 μg 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-μg) 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.
authors.affiliation: *Division of Infectious Diseased and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA;†Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA;‡Division of Infectious Diseases, University of Colorado, Denver, CO;§Division of Infectious Diseases, University of Pennsylvania, Philadelphia, PA;‖Profectus BioSciences, Inc., Tarrytown, NY;¶Department of Immunology and Microbiology, Rush University School of Medicine, Chicago, IL;#Department of Neurology, Washington University School of Medicine, St. Louis, MO;**HIV/AIDS Division, University of California, San Francisco, CA;††Social and Scientific Systems, Inc., Silver Springs, MD;‡‡Division of AIDS, NIAID, Bethesda, MD;§§Frontier Science, Amherst, NY; and‖‖Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.forename: Cara C
authors.initials: CC
authors.lastname: Wilson
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Roy M
authors.initials: RM
authors.lastname: Matining
authors.forename: Michael A
authors.initials: MA
authors.lastname: Egan
authors.forename: John
authors.initials: J
authors.lastname: Eldridge
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Anne F
authors.initials: AF
authors.lastname: Luetkemeyer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tiu
authors.forename: Ana L
authors.initials: AL
authors.lastname: Martinez
authors.forename: Jennifer
authors.initials: J
authors.lastname: Janik
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Spitz
authors.forename: John
authors.initials: J
authors.lastname: Hural
authors.forename: Juliana
authors.initials: J
authors.lastname: McElrath
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D018274:Electroporation; D005260:Female; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015488:HIV Antigens; D007376:Interleukin-2; D019444:Vaccines, DNA; D018664:Interleukin-12; D007371:Interferon-gamma