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DNA represents an ideal vaccine platform for HIV and many infectious diseases because of its safety, stability, and ease of manufacture. However, the immunogenicity of DNA vaccines has traditionally been low compared with viral vectors, recombinant protein, and live attenuated vaccines. The immunogenicity of DNA vaccines has been significantly enhanced by delivery with in vivo electroporation. Further improvements now allow electroporation to be performed in the dermis, which could potentially improve patient tolerability and may further enhance immunogenicity. In this study we examined how the current of intradermal vaccination impacts antigen expression, inflammation, and the induction of both humoral and cellular immunity in guinea pigs and nonhuman primates. We observed that a lower (0.1 A) current reduced inflammation and improved antigen expression compared with a 0.2 A current. The improved antigen expression resulted in a trend toward higher cellular immune responses but no impact on HIV- and influenza-specific binding titers. This study highlights the need for optimization of electroporation conditions in vivo in order to balance enhanced plasmid transfection with a loss of expression due to tissue inflammation and necrosis. These results suggest that a lower, 0.1-A current may not only improve patient tolerability but also improve immunogenicity.

human gene therapy

Intradermal DNA Vaccination Enhanced by Low-Current Electroporation Improves Antigen Expression and Induces Robust Cellular and Humoral Immune Responses