Immunization via hair follicles by topical application of naked DNA to normal skin


In order to test the immune response generated to small amounts of foreign protein in skin, we applied naked DNA in aqueous solution to untreated normal skin. Topical application of plasmid expression vectors for lacZ and the hepatitis B surface antigen (HBsAg) to intact skin induced antigen-specific immune responses that displayed TH2 features. For HBsAg, specific antibody and cellular responses were induced to the same order of magnitude as those produced by intramuscular injection of the commercially available recombinant HBsAg polypeptide vaccine. Finally, topical gene transfer was dependent on the presence of normal hair follicles.

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Figure 1: Effect of vector and gene delivery routes on induction of antibody responses.
Figure 2: Topical application of plasmid DNA encoding HBsAg.
Figure 3: Normal hair follicles are required for topical gene transfer to untreated skin.


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This work was supported by the Office of Research and Development, Department of Veterans Affairs (VA), by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) to P.A.K, and by the Herzog Foundation. H.F. is a recipient of an NIH postdoctoral training fellowship. We thank M. Kay for adenoviral vectors, X. He and H. Greenberg for HBsAg cDNA, and N. Griffiths and P. Bernstein for administrative support.

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Correspondence to Paul A. Khavari.

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