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. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Yu Z, Chung W-G, Sloat BR, Löhr CV, Weiss R, B Rodriguez L, Li X, Cui Z |
Journal | J Pharm Pharmacol |
Volume | 63 |
Issue | 2 |
Pagination | 199-205 |
Date Published | 2011 Feb |
ISSN | 2042-7158 |
Keywords | Administration, Cutaneous, Animals, beta-Galactosidase, DNA, Female, Hair Follicle, Hair Removal, Immunization, Mice, Mice, Inbred BALB C, Plasmids, Skin, Skin Absorption, Tetradecanoylphorbol Acetate, Tretinoin, Vaccines, DNA |
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. |
DOI | 10.1111/j.2042-7158.2010.01219.x |
Alternate Journal | J. Pharm. Pharmacol. |
PubMed ID | 21235583 |
PubMed Central ID | PMC3148656 |
Grant List | R01 AI078304-02 / AI / NIAID NIH HHS / United States AI065774 / AI / NIAID NIH HHS / United States R03 AI065774 / AI / NIAID NIH HHS / United States AI078304 / AI / NIAID NIH HHS / United States R01 AI078304-05 / AI / NIAID NIH HHS / United States R01 AI078304-04 / AI / NIAID NIH HHS / United States R01 AI078304-03 / AI / NIAID NIH HHS / United States R01 AI078304-01A1 / AI / NIAID NIH HHS / United States R01 AI078304 / AI / NIAID NIH HHS / United States |