title: Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery.
abstract: BACKGROUND
  DNA vaccines have been very poorly immunogenic in humans but have been an effective priming modality in prime-boost regimens. Methods to increase the immunogenicity of DNA vaccines are needed.
  
  
  METHODS
  HIV Vaccine Trials Network (HVTN) studies 070 and 080 were multicenter, randomized, clinical trials. The human immunodeficiency virus type 1 (HIV-1) PENNVAX®-B DNA vaccine (PV) is a mixture of 3 expression plasmids encoding HIV-1 Clade B Env, Gag, and Pol. The interleukin 12 (IL-12) DNA plasmid expresses human IL-12 proteins p35 and p40. Study subjects were healthy HIV-1-uninfected adults 18-50 years old. Four intramuscular vaccinations were given in HVTN 070, and 3 intramuscular vaccinations were followed by electroporation in HVTN 080. Cellular immune responses were measured by intracellular cytokine staining after stimulation with HIV-1 peptide pools.
  
  
  RESULTS
  Vaccination was safe and well tolerated. Administration of PV plus IL-12 with electroporation had a significant dose-sparing effect and provided immunogenicity superior to that observed in the trial without electroporation, despite fewer vaccinations. A total of 71.4% of individuals vaccinated with PV plus IL-12 plasmid with electroporation developed either a CD4(+) or CD8(+) T-cell response after the second vaccination, and 88.9% developed a CD4(+) or CD8(+) T-cell response after the third vaccination.
  
  
  CONCLUSIONS
  Use of electroporation after PV administration provided superior immunogenicity than delivery without electroporation. This study illustrates the power of combined DNA approaches to generate impressive immune responses in humans.
authors.affiliation: Infectious Diseases Division, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. s.kalams@vanderbilt.edu
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.forename: Scott D
authors.initials: SD
authors.lastname: Parker
authors.forename: Marnie
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authors.lastname: Elizaga
authors.forename: Barbara
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authors.lastname: Metch
authors.forename: Srilatha
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authors.lastname: Edupuganti
authors.forename: John
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authors.lastname: Hural
authors.forename: Stephen
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authors.lastname: De Rosa
authors.forename: Donald K
authors.initials: DK
authors.lastname: Carter
authors.forename: Kyle
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authors.lastname: Rybczyk
authors.forename: Ian
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authors.lastname: Frank
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fuchs
authors.forename: Beryl
authors.initials: B
authors.lastname: Koblin
authors.forename: Denny H
authors.initials: DH
authors.lastname: Kim
authors.forename: Patrice
authors.initials: P
authors.lastname: Joseph
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: John
authors.initials: J
authors.lastname: Eldridge
authors.forename: Jean
authors.initials: J
authors.lastname: Boyer
authors.forename: Adam
authors.initials: A
authors.lastname: Sherwat
authors.forename: Massimo
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authors.lastname: Cardinali
authors.forename: Mary
authors.initials: M
authors.lastname: Allen
authors.forename: Michael
authors.initials: M
authors.lastname: Pensiero
authors.forename: Chris
authors.initials: C
authors.lastname: Butler
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.forename: James G
authors.initials: JG
authors.lastname: Kublin
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D004333:Drug Administration Routes; D018274:Electroporation; D005260:Female; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D014611:Vaccination / Q000379:methods; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D018664:Interleukin-12; D004247:DNA
keywords: electroporation; plasmid cytokine adjuvant; vaccination