Single chain antibody fragments for the selective targeting of antigens to dendritic cells.
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.
Demangel
Caroline
C
Centenary Institute of Cancer Medicine and Cell Biology, Newtown, Australia. demangel@pasteur.fr
Zhou
Jie
J
Choo
Andre B H
AB
Shoebridge
Grant
G
Halliday
Gary M
GM
Britton
Warwick J
WJ
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*
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