Enhancing DNA Vaccine Potency by Combining a Strategy to Prolong Dendritic Cell Life and Intracellular Targeting Strategies with a Strategy to Boost CD4+ T Cells

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Abstract
Intradermal administration of DNA vaccines, using a gene gun, represents an effective means of delivering DNA directly into professional antigen-presenting cells (APCs) in the skin and thus allows the application of strategies to modify the properties of APCs to enhance DNA vaccine potency. In the current study, we hypothesized that the potency of human papillomavirus (HPV) type 16 E7 DNA vaccines employing intracellular targeting strategies combined with a strategy to prolong the life of dendritic cells (DCs) could be further enhanced by the addition of a DNA vaccine capable of generating high numbers of pan-HLA-DR reactive epitope (PADRE)-specific CD4+ T cells. We observed that the addition of PADRE DNA to E7 DNA vaccines employing intracellular targeting strategies with a strategy to prolong the life of DCs led to significant enhancement of E7-specific CD8+ effector and memory T cells as well as significantly improved therapeutic effects against established E7-expressing tumors in tumor-challenged mice. Our data suggest that the potency of a DNA vaccine combining an intracellular targeting strategy as well as a strategy to prolong the life of DCs can be further enhanced by addition of DNA that is capable of generating high numbers of PADRE-specific CD4+ T cells.