Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation

Abstract

Recently it has become clear that more potent methods for DNA vaccine delivery need to be developed to enhance the efficacy of DNA vaccines. In vivo electroporation has emerged as a potent method for DNA vaccine delivery. In a mouse model, we evaluated the CD8(+) T lymphocyte response to a prostate cancer DNA vaccine encoding prostate-specific antigen (PSA) after intradermal electroporation. A significantly increased gene expression (100- to 1000-fold) and higher levels of PSA-specific T cells, compared to DNA delivery without electroporation, was demonstrated. Interestingly, investigation of a panel of different electroporation conditions showed that only some conditions that induce high levels of gene expression additionally induced cellular immunity. This suggests that electroporation parameters should be carefully optimized, not only to enhance transfection efficiency, but also to enhance the immune response to the vaccine. This study demonstrates the applicability of intradermal electroporation as a delivery method for genetic cancer vaccines and other DNA vaccines relying on antigen-specific T cell induction.

Duration and level of transgene expression after gene electrotransfer to skin in mice

“…Studies with DNA vaccinations in animal models have shown promising results in infectious diseases such as hepatitis B, [24][25][26][27] HIV, 28 malaria 29 and smallpox. 30 Vaccination studies using intradermal electroporation in mice with DNA coding for prostate-specific antigen (PSA) gave increased level of PSA-specific T cells 31,32 and a Phase I/II clinical trial (NCT00859729) is currently running.…”

Simultaneous Targeting of Multiple Hemagglutinins to APCs for Induction of Broad Immunity against Influenza

“…In addition, a positive control group was vaccinated with anti-MHCII-H1(PR8) (18). The vaccine plasmids were delivered intradermally in combination with EP to secure efficient cellular uptake of DNA (11,30). Following vaccination, sera were monitored for the development of Abs against recombinant HA from H5, H6, H8, H9, H11, H13, and H1(PR8) influenza viruses.…”

“…However, DNA vaccines are typically hampered by low immunogenicity, particularly in larger animals and humans. To remedy this shortcoming, better methods of DNA delivery have been developed (11)(12)(13). However, the improvements have typically been restricted to more efficient DNA uptake by cells at the site of delivery.…”

DNA Vaccines against Infectious Diseases and Cancer

“…Further co-injection of PSA DNA vaccines with DNA expressing IL-2 and GM-CSF induced a significant level of Ag-specific CTL and antitumor responses to PSA-expressing tumors (Roos et al, 2005). More recently, ID-EP has been demonstrated to be a more effective way to induce PSA-specific immune responses (Roos et al, 2006). In the study, ID-EP delivery increased PSA gene expression (100-to 1,000-fold) and induced higher levels of Ag-specific T cells, compared to DNA delivery without EP.…”