title: The extent of the uptake of plasmid into the skin determines the immune responses induced by a DNA vaccine applied topically onto the skin.
abstract: OBJECTIVE
  Non-invasive immunization by application of plasmid DNA topically onto the skin is an attractive immunization approach. However, the immune responses induced are generally weak. Previously, we showed that the antibody responses induced by topical DNA vaccine are significantly enhanced when hair follicles in the application area are induced into the anagen (growth) stage by hair plucking. In the present study, we further investigated the mechanism of immune enhancement.
  
  
  METHODS
  Three different methods--hair plucking or treatment with retinoic acid (RA) or O-tetradecanoylphorbol-13-acetate (TPA)--were used to induce mice hair follicles into the anagen stage before they were dosed with a β-galactosidase-encoding plasmid, and the specific antibody responses induced were evaluated.
  
  
  RESULTS
  The hair-plucking method was more effective at enhancing the resultant antibody responses. Treatment with RA or TPA caused more damage to the skin and induced more severe local inflammation than hair plucking. However, hair plucking was most effective at enhancing the uptake or retention of the DNA in the application area.
  
  
  CONCLUSIONS
  The uptake of plasmid DNA in the application area correlated with the antibody responses induced by a topically applied DNA.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.forename: Woon-Gye
authors.initials: WG
authors.lastname: Chung
authors.forename: Brian R
authors.initials: BR
authors.lastname: Sloat
authors.forename: Christiane V
authors.initials: CV
authors.lastname: Löhr
authors.forename: Richard
authors.initials: R
authors.lastname: Weiss
authors.forename: B Leticia
authors.initials: BL
authors.lastname: Rodriguez
authors.forename: Xinran
authors.initials: X
authors.lastname: Li
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004247:DNA / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D005260:Female; D018859:Hair Follicle / Q000187:drug effects / Q000378:metabolism; D006204:Hair Removal / Q000379:methods; D007114:Immunization / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
chemical_list: D019444:Vaccines, DNA; D014212:Tretinoin; D004247:DNA; D001616:beta-Galactosidase; D013755:Tetradecanoylphorbol Acetate