1. ^*Inex Pharmaceuticals Corporation, Burnaby, British Columbia, Canada
2. ^†Departments of Medicine and BC Research Institute of Children and Women's Health, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence: Dr Jan P. Dutz, The Skin Care Center, 835 West Tenth Avenue, Vancouver, British Columbia, Canada V5Z 4E8. Email: dutz@interchange.ubc.ca

Received 22 April 2002; Revised 6 November 2003; Accepted 26 November 2003.

Abstract

Immunostimulatory oligodeoxynucleotides (ODN) are effective adjuvants in the induction of humoral and cellular immune responses when administered parenterally with antigen. The skin has recently become a target organ for the design of non-invasive vaccine technologies. Using ovalbumin (OVA) as a model antigen, we demonstrate that the application of ODN sequences to tape-stripped skin promotes the induction of potent cytotoxic T lymphocyte (CTL) responses to co-administered peptide. Induction of peptide-specific CTL required the presence of CpG motifs within the ODN. CTL afforded tumor protection against a tumor expressing an immunodominant OVA CTL epitope. CTL could also be induced to whole protein administered onto the skin. Differential CpG sequence activity was noted with respect to the induction of CTL to epicutaneous protein with an ODN sequence containing a poly-G motif having an optimal effect. Peptide-specific CTL could be detected in the peripheral blood as early as 6 d after a single immunization. These results highlight the potential of the bare skin as a route for vaccine development and indicate an important role for immunostimulatory ODN as adjuvants to generate functional CTL with the help of the skin immune system.