title: A multi-head intradermal electroporation device allows for tailored and increased dose DNA vaccine delivery to the skin.
abstract: The identification of an effective and tolerable delivery method is a necessity for the success of DNA vaccines in the clinic. This manuscript describes the development and validation of a multi-headed intradermal electroporation device which would be applicable for delivering multiple DNA vaccine plasmids simultaneously but spatially separated. Reporter gene plasmids expressing green and red fluorescent proteins were used to demonstrate the impact of spatial separation on DNA delivery to increase the number of transfected cells and avoid interference through visible expression patterns. To investigate the impact of plasmid interference on immunogenicity, a disease target was investigated where issues with multi-valent vaccines had been previously described. DNA-based Hantaan and Puumala virus vaccines were delivered separately or as a combination and the effect of multi-valence was determined by appropriate assays. While a negative impact was observed for both antigenic vaccines when delivered together, these effects were mitigated when the vaccine was delivered using the multi-head device. We also demonstrate how the multi-head device facilitates higher dose delivery to the skin resulting in improved immune responses. This new multi-head platform device is an efficient, tolerable and non-invasive method to deliver multiple plasmid DNA constructs simultaneously allowing the tailoring of delivery sites for combination vaccines. Additionally, this device would allow the delivery of multi-plasmid vaccine formulations without risk of impacted immune responses through interference. Such a low-cost, easy to use device platform for the delivery of multi-agent DNA vaccines would have direct applications by the military and healthcare sectors for mass vaccination purposes.
authors.affiliation: a Inovio Pharmaceuticals Inc. ; Plymouth Meeting , PA USA.
authors.forename: Jay R
authors.initials: JR
authors.lastname: McCoy
authors.forename: Janess M
authors.initials: JM
authors.lastname: Mendoza
authors.forename: Kristin W
authors.initials: KW
authors.lastname: Spik
authors.forename: Catherine
authors.initials: C
authors.lastname: Badger
authors.forename: Alan F
authors.initials: AF
authors.lastname: Gomez
authors.forename: Connie S
authors.initials: CS
authors.lastname: Schmaljohn
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.forename: Kate E
authors.initials: KE
authors.lastname: Broderick
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D006224:Cricetinae; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D018274:Electroporation / Q000295:instrumentation* / Q000379:methods; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006168:Guinea Pigs; D018063:Hantaan virus / Q000276:immunology; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology / Q000517:prevention & control; D007271:Injections, Intradermal / Q000379:methods; D008164:Luminescent Proteins / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D029262:Puumala virus / Q000276:immunology; D012867:Skin; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000097573:Red Fluorescent Protein
chemical_list: D000914:Antibodies, Viral; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D019444:Vaccines, DNA; D014765:Viral Vaccines; D000097573:Red Fluorescent Protein
keywords: DNA vaccine; dermal; electroporation; multi-agent; noninvasive; tolerable