A versatile bifunctional dendritic cell targeting vaccine vector.

We have developed an efficient versatile in vivo dendritic cell (DC) targeting vector for delivering different classes of antigens such as proteins, peptide, glycolipids and naked DNA for vaccine applications. A single chain antibody (scFv) that recognizes DEC-205 receptor of DC was fused with a core-streptavidin domain and expressed in Escherichia coli using the T7 expression system. The bifunctional fusion protein (bfFp) was expressed as a periplasmic soluble protein and affinity-purified in its monomeric form. The bifunctional activity against DEC-205 and biotin was characterized by ELISA and Western blot. In vivo DC targeting of a diverse group of biotinylated antigens such as viral and bacterial proteins, a cancer peptide, gangliosides and DNA of certain infectious diseases was conducted in mice. Results show that in the presence of bfFp and costimulatory anti-CD40 mAb, both humoral and cell-mediated responses were augmented in either the single antigen or multiple antigen targeting strategy. Lastly, bfFp based DC targeting of antigens in low doses may be a useful strategy for the design of monovalent or polyvalent vaccines for the masses.