Safety and Comparative Immunogenicity of an HIV-1 DNA Vaccine in Combination with Plasmid Interleukin 12 and Impact of Intramuscular Electroporation for Delivery

Infectious Diseases Division, Department of Medicine.
The Journal of Infectious Diseases (Impact Factor: 6). 07/2013; 208(5). DOI: 10.1093/infdis/jit236
Source: PubMed


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.

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.

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.

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.

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Available from: Jonathan Fuchs, Nov 16, 2015
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    • "Live-attenuated vaccines showed promising levels of protection in NHP models [13] [15]; however, they were associated with irreversible integration in the host genome, persistence and reversion to pathogenic state in some vaccinated animals [16] [17] impelling safer strategies for clinical use. Alternatively, DNA vaccines became more attractive tools for vaccination against HIV and other pathogens, particularly with effort being made to increase their immunogenicity via optimizing vaccine design, use of adjuvants , and delivery methods [43] [44] [45] [46] [47]. "
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    • "The CD4+ and CD8+ T-cell subsets producing IFN-γ or IL-2 (IL2.IFNg) are used by the HVTN as the readouts for the ICS assay. We note that we detect an antigen-specific response in these subsets and that the CD4 subsets have the strongest response to antigen stimulation by both methods, consistent with the original study findings [32],[33]. Most importantly, there are no significant differences between the manual and OpenCyto gating results for any of the cell subsets (two-sided paired Wilcoxon test). "
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