TitleThe extent of the uptake of plasmid into the skin determines the immune responses induced by a DNA vaccine applied topically onto the skin.
Publication TypeJournal Article
Year of Publication2011
AuthorsYu Z, Chung W-G, Sloat BR, Löhr CV, Weiss R, B Rodriguez L, Li X, Cui Z
JournalJ Pharm Pharmacol
Volume63
Issue2
Pagination199-205
Date Published2011 Feb
ISSN2042-7158
KeywordsAdministration, 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.

DOI10.1111/j.2042-7158.2010.01219.x
Alternate JournalJ. Pharm. Pharmacol.
PubMed ID21235583
PubMed Central IDPMC3148656
Grant ListR01 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