Transcriptional targeting of dendritic cells – a promising strategy to improve the efficiency of DNA vaccines.

Stephan Sudowe, Ralf Ross, Isis Ludwig-Portugall, Evelyn Montermann, Matthias Bros and Angelika B. Reske-Kunz.

Clinical Research Unit Allergology, Department of Dermatology, Johannes Gutenberg-University, D-55101 Mainz, Germany.

e-mail: sudowe@mail.uni-mainz.de

Due to the outstanding primary stimulatory capacity of dendritic cells (DC), targeting of antigen to DC represents an essential requirement for the development of efficient strategies for immune therapy. We transcriptionally targeted endogenous antigen synthesis selectively to DC by transfection with plasmid DNA expressing reporter genes under control of the promoter of the fascin gene (pFascin). In vitro analysis of transgene expression revealed specificity for mature DC and few other nonhaematopoietic cell types. We examined the efficiency of in vivo transfection with pFascin by gene gun-mediated DNA immunization of mice. Transfected cells in skin and draining lymph nodes were identified as Langerhans cells by means of the expression of Langerin (CD207). Biolistic transfection with pFascin induced a distinct T helper 1 immune response and led to the recruitment of CD8+ cytotoxic T cells. Since these two features are known to play prominent roles in the counter-regulation of IgE synthesis, we examined the potency of genetic vaccination with antigen-encoding pFascin to modulate specific IgE antibody (Ab) responses in a mouse model of type I allergy. IgE Ab production was effectively inhibited by prophylactic gene gun-mediated vaccination as well as by intervening vaccinations in a therapeutical setting. Thus, the strategy of focusing endogenous antigen production specifically to DC by virtue of transcriptional targeting utilizing the fascin promoter might provide new opportunities for the development of efficient DNA vaccines.