title: Skin Transfection Patterns and Expression Kinetics of Electroporation-Enhanced Plasmid Delivery Using the CELLECTRA-3P, a Portable Next-Generation Dermal Electroporation Device.
abstract: The CELLECTRA-3P dermal electroporation device (Inovio Pharmaceuticals, Plymouth Meeting, PA) has been evaluated in the clinic and shown to enhance the delivery of an influenza DNA vaccine. To understand the mechanism by which this device aids in enhancing the host immune response to DNA vaccines we investigated the expression kinetics and localization of a reporter plasmid (pGFP) delivered via the CELLECTRA-3P. Histological analysis revealed green fluorescent protein (GFP) expression as early as 1 hr posttreatment in the epidermal and dermal layers, and as early as 2 hr posttreatment in the subdermal layers. Immunofluorescence techniques identified keratinocytes, fibrocytes, dendritic-like cells, adipocytes, and myocytes as the principal cell populations transfected. We proceeded to demonstrate elicitation of robust host immune responses after plasmid DNA (pDNA) vaccination. In guinea pigs equivalent humoral (antibody binding titers) immune responses were observed between protocols using either CELLECTRA-3P or intramuscular electroporation to deliver the DNA vaccine. In nonhuman primates, robust interferon-γ enzyme-linked immunospot and protective levels of hemagglutination inhibition titers after pDNA vaccination were observed in groups treated with the CELLECTRA-3P. In conclusion, these findings may assist in the future to design efficient, tolerable DNA vaccination strategies for the clinic.
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania.
authors.forename: Dinah H
authors.initials: DH
authors.lastname: Amante
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania.
authors.forename: Trevor R F
authors.initials: TR
authors.lastname: Smith
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania.
authors.forename: Janess M
authors.initials: JM
authors.lastname: Mendoza
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania.
authors.forename: Katherine
authors.initials: K
authors.lastname: Schultheis
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania.
authors.forename: Jay R
authors.initials: JR
authors.lastname: McCoy
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania.
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania.
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Broderick
mesh_terms: D000818:Animals; D020405:Dermis / Q000378:metabolism; D018274:Electroporation / Q000295:instrumentation* / Q000379:methods*; D004817:Epidermis / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006168:Guinea Pigs; D008253:Macaca mulatta; D018482:Muscle, Skeletal / Q000378:metabolism; D010957:Plasmids / Q000235:genetics*; D012867:Skin / Q000378:metabolism*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D019444:Vaccines, DNA; D049452:Green Fluorescent Proteins