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Research Paper

High Efficiency Transduction of Dendritic Cells by Adenoviral Vectors Targeted to DC-SIGN

Nikolay Korokhov, Tanja D. de Gruijl, Wayne A. Aldrich, Pierre L. Triozzi, Papia T. Banerjee, Stephen D. Gillies, Tyler J. Curiel, Joanne T. Douglas|, Rik J. Scheper, David T. Curiel

volume 4 | issue 3

march 2005
Pages: 289-294

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Dendritic cells (DCs) are a central element in the development of antigen-specific immune responses. The lack of a specific and efficient technique for the in vivo delivery of antigens to DCs remains a major obstacle limiting a vaccine’s ability to induce an effective immune response. The efficacy of adenoviral (Ad) vectors in this regard can be enhanced through alterations in vector tropism such that DC-targeted transduction is achieved. Here, the efficiency of DC transduction by Ad vectors retargeted to DC-specific ICAM-3 grabbing non-integrin (DC-SIGN) was studied and compared to that of Ad vectors retargeted through CD40. A comparable and significant enhancement of gene transfer to monocyte derived DCs (MDDCs) was accomplished by means of an Ad vector harboring the Fc-binding domain of Staphylococcus aureus protein A in combination with antibodies to DC-SIGN or to CD40 or with fused complexes of human Ig-Fc with their natural ligands, i.e. ICAM-3 or CD40L, respectively. Whereas CD40-targeted Ad transduction resulted in a more profound phenotypic DC maturation, DC-SIGN- and CD40-targeted Ad both induced similar levels of IL-12 secretion. These data demonstrate the usefulness of DC-SIGN as a DC-restricted targeting motif for Ad-mediated vaccination strategies.




We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.