Original Article

Subject Category: Vaccine Technology

Molecular Therapy (2007) 15 11, 2037–2043. doi:10.1038/sj.mt.6300286

Immunization by Application of DNA Vaccine onto a Skin Area Wherein the Hair Follicles Have Been Induced into Anagen-onset Stage

Dalia S Shaker1, Brian R Sloat1, Uyen M Le1, Christiane V Löhr2, Nijaporn Yanasarn1, Kay A Fischer2 and Zhengrong Cui1

  1. 1Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA
  2. 2Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA

Correspondence: Zhengrong Cui, Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA. E-mail: Zhengrong.cui@oregonstate.edu

Received 2 February 2007; Accepted 16 July 2007; Published online 14 August 2007.

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Abstract

An attractive approach to immunization is to apply DNA vaccine topically onto the skin. However, it is important to ensure that a strong immune response is induced without disrupting the skin stratum corneum. The hair follicles have been shown to be the major portal of entry for DNA applied onto the skin, and it has been reported that the transfection of hair follicle cells occurs mainly at the onset of a new growing stage of the hair cycle. Using an anthrax protective antigen (PA) protein-encoding plasmid in mice, we demonstrated that the anti-PA immune responses were significantly stronger when the hair follicles in the application area were induced into anagen-onset stage than when in telogen stage. The anti-PA antibodies enabled the immunized mice to survive a lethal dose of anthrax lethal toxin challenge. The enhanced immune responses can be partially attributed to the enhanced antigen gene expression and plasmid DNA uptake in the skin area wherein the hair follicles were induced into anagen-onset stage. Moreover, the moderate dermal inflammation associated with the anagen induction may also have contributed to the enhancement of the resultant immune response. This represents a novel approach to enhancing the immune response induced by a topically applied DNA vaccine.

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