Skin Electrovaccination: Effects on Transgene Expression, DNA Persistence and Local Tissue Environment

Background: The use of electrical pulses to enhance uptake of molecules into living cells have been used for decades. This technique, often referred to as electroporation, has become an increasingly popular method to enhance in vivo DNA delivery for both gene. therapy applications as well as for delivery of vaccines against both infectious diseases and cancer. In vivo electrovaccination is currently being investigated in several clinical trials, including DNA delivery to healthy volunteers. However, the mode of action at molecular level is not yet fully understood. Methodology/Principal Findings: This study investigates intradermal DNA electrovaccination in detail and describes the effects on expression of the vaccine antigen, plasmid persistence and the local tissue environment. Gene profiling of the vaccination site is currently being evaluated in clinical trials, the data provided will be of high significance.. Conclusions/Significance: This study provides important insights to how DNA delivery by intradermal electrovaccination affects the local immunological responses of the skin, transgene expression and clearance of the plasmid. As the described vaccination approach showed that the combination of DNA and electroporation induced a significant up-regulation of pro-inflammatory genes. In vivo imaging of luciferase activity after electrovaccination demonstrated a rapid onset (minutes) and a long duration (months) of transgene expression. However, when the more immunogenic prostate specific antigen (PSA) was co-administered, PSA-specific T cells were induced and concurrently the luciferase expression became undetectable. Electroporation did not affect the long-term persistence of the PSA-expressing plasmid. untreated mice (n=4), and mice subjected to DNA vaccination followed by electroporation (n=3)