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

Objectives 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. Key findings 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. © 2011 Royal Pharmaceutical Society.