1. ^*Division of Immnunology, Allergy, and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria
2. ^†CeMM-Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria
3. ^‡Department of Dermatology, University of Duisburg/Essen, Germany

Correspondence: Stephan N. Wagner, Division of Immnunology, Allergy, and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria. Email: Stephan.Wagner@akh-wien.ac.at

Received 25 November 2003; Revised 23 January 2004; Accepted 14 February 2004; Published online 6 July 2004.

Abstract

DNA vaccines can induce impressive specific cellular immune response (IR) when taking advantage of their recognition as pathogen-associated molecular patterns (PAMP) through Toll-like receptors (TLR) expressed on/in cells of the innate immune system. Among the many types of PAMP, immunostimulatory DNA, so-called CpG motifs, was shown to interact specifically with TLR9, which is expressed in plasmacytoid dendritic cells (pDC), a key regulatory cell for the activation of innate and adaptive IR. We now report that CpG motifs, when introduced into the backbone, are a useful adjuvant for plasmid-based DNA (pDNA) vaccines to induce melanoma antigen-specific protective T cell responses in the Cloudman M3/DBA/2 model. The CpG-enriched pDNA vaccine induced protection against subsequent challenge with melanoma cells at significantly higher levels than its parental unmodified vector. Preferential induction of an antigen-specific, protective T cell response could be demonstrated by (i) induction of antigen-dependent tumor cell protection, (ii) complete loss of protection by in vivo CD4⁺/CD8⁺T cell- but not NK cell-depletion, and (iii) the detection of antigen-specific T cell responses but not of relevant NK cell activity in vitro. These results demonstrate that employing PAMP in pDNA vaccines improves the induction of protective, antigen-specific, T cell-mediated IR.