title: DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response.
abstract: The immunocompetence and clinical accessibility of dermal tissue offers an appropriate and attractive target for vaccination. We previously demonstrated that pDNA injection into the skin in combination with surface electroporation (SEP), results in rapid and robust expression of the encoded antigen in the epidermis. Here, we demonstrate that intradermally EP-enhanced pDNA vaccination results in the rapid induction of a host humoral immune response. In the dermally relevant guinea pig model, we used high-resolution laser scanning confocal microscopy to observe direct dendritic cell (DC) transfections in the epidermis, to determine the migration kinetics of these cells from the epidermal layer into the dermis, and to follow them sequentially to the immediate draining lymph nodes. Furthermore, we delineate the relationship between the migration of directly transfected epidermal DCs and the generation of the host immune response. In summary, these data indicate that direct presentation of antigen to the immune system by DCs through SEP-based in vivo transfection in the epidermis, is related to the generation of a humoral immune response.
authors.affiliation: Inovio Pharmaceuticals , San Diego, California, USA.
authors.forename: Trevor Rf
authors.initials: TR
authors.lastname: Smith
authors.affiliation: Inovio Pharmaceuticals , San Diego, California, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Schultheis
authors.affiliation: The Scripps Research Institute, Core Microscopy Facility , La Jolla, California, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Kiosses
authors.affiliation: Inovio Pharmaceuticals , San Diego, California, USA.
authors.forename: Dinah H
authors.initials: DH
authors.lastname: Amante
authors.affiliation: Inovio Pharmaceuticals , San Diego, California, USA.
authors.forename: Janess M
authors.initials: JM
authors.lastname: Mendoza
authors.affiliation: Inovio Pharmaceuticals , San Diego, California, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Stone
authors.affiliation: Inovio Pharmaceuticals , San Diego, California, USA.
authors.forename: Jay R
authors.initials: JR
authors.lastname: McCoy
authors.affiliation: Inovio Pharmaceuticals , San Diego, California, USA.
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.affiliation: Inovio Pharmaceuticals , San Diego, California, USA.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Broderick