title: DNA vaccine delivery by densely-packed and short microprojection arrays to skin protects against vaginal HSV-2 challenge.
abstract: There is an unmet medical need for a prophylactic vaccine against herpes simplex virus (HSV). DNA vaccines and cutaneous vaccination have been tried for many applications, but few reports combine this vaccine composition and administration route. We compared DNA administration using the Nanopatch™, a solid microprojection device coated with vaccine comprised of thousands of short (110 μm) densly-packed projections (70 μm spacing), to standard intramuscular DNA vaccination in a mouse model of vaginal HSV-2 infection. A dose-response relationship was established for immunogenicity and survival in both vaccination routes. Appropriate doses administered by Nanopatch™ were highly immunogenic and enabled mouse survival. Vaginal HSV-2 DNA copy number day 1 post challenge correlated with survival, indicating that vaccine-elicited acquired immune responses can act quickly and locally. Solid, short, densely-packed arrays of microprojections applied to the skin are thus a promising route of administration for DNA vaccines.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Angela Shaulov
authors.initials: AS
authors.lastname: Kask
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Chen
authors.forename: Joshua O
authors.initials: JO
authors.lastname: Marshak
authors.forename: Lichun
authors.initials: L
authors.lastname: Dong
authors.forename: Misty
authors.initials: M
authors.lastname: Saracino
authors.forename: Dexiang
authors.initials: D
authors.lastname: Chen
authors.forename: Courtney
authors.initials: C
authors.lastname: Jarrahian
authors.forename: Mark A
authors.initials: MA
authors.lastname: Kendall
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000032:analysis; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000502:physiology; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014621:Vagina / Q000821:virology*; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D022301:Herpes Simplex Virus Vaccines; D007074:Immunoglobulin G; D019444:Vaccines, DNA