Recombinant adenovirus type 5 vectors that target DC-SIGN, ChemR23 and αvβ3 integrin efficiently transduce human dendritic cells and enhance presentation of vectored antigens

Recombinant adenoviruses (rAds) represent a promising system for vaccine delivery but transduce dendritic cells (DC) relatively poorly. To address this concern, we used a biotin–avidin linkage to conjugate rAd vectors to ligands which bind with high affinity to selected receptors on DC (ChemR23, αvβ3 integrin, and DC-SIGN). The targeted vectors had an enhanced ability to transduce human monocyte-derived DC compared to untargeted virus. In addition, DC transduced with targeted rAd vectors were more efficient at stimulating cytokine production by autologous memory CD8+ T cells, against a vector-encoded antigen. These results expand the range of cell surface receptors that can be used to target rAd5 vectors to DC, and may facilitate future development of rAd-based vaccines.