title: Single chain antibody fragments for the selective targeting of antigens to dendritic cells.
abstract: In order to target antigens (Ags) selectively to dendritic cells (DC), we derived single chain antibody fragments (scFvs) from NLDC-145 and N418, two monoclonal antibodies binding the mouse dendritic cell-restricted surface molecules DEC-205 and CD11c. Recombinant hexahistidine-tagged forms of the scFvs (scNLDC and scN418) were efficiently produced in a baculovirus expression system. Both scFvs bound DEC-205(+) Langerhans cells and CD11c(+) fetal skin-derived dendritic cells (FSDCs) comparably to their parental antibodies. Immunization of C57BL/6 mice with a DNA vaccine encoding a model protein antigen fused to scNLDC stimulated specific immune responses in both the humoral and cellular compartments, in contrast to DNA vaccines expressing scN418-targeted or untargeted antigen. Our results show that antigen targeting to DCs via a DEC-205 binding scFv leads to enhanced immunogenicity. Further, this work suggests that scFvs fused to protein antigens and delivered as DNA vaccines may provide a generic means for delivering vaccinal molecules to selected cell populations.
authors.affiliation: Centenary Institute of Cancer Medicine and Cell Biology, Newtown, Australia. demangel@pasteur.fr
authors.forename: Caroline
authors.initials: C
authors.lastname: Demangel
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Andre B H
authors.initials: AB
authors.lastname: Choo
authors.forename: Grant
authors.initials: G
authors.lastname: Shoebridge
authors.forename: Gary M
authors.initials: GM
authors.lastname: Halliday
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D039521:CD11c Antigen / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D007128:Immunoglobulin Fragments / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D051379:Mice; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039521:CD11c Antigen; C093569:DEC-205 receptor; D007128:Immunoglobulin Fragments; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface