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J Infect Dis. 2013 Sep 1;208(5):818-29. doi: 10.1093/infdis/jit236. Epub 2013 Jul 8.

Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery.

Author information

1
Infectious Diseases Division, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. s.kalams@vanderbilt.edu

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.

KEYWORDS:

electroporation; plasmid cytokine adjuvant; vaccination

PMID:
23840043
PMCID:
PMC3733506
DOI:
10.1093/infdis/jit236
[Indexed for MEDLINE]
Free PMC Article

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