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 s...

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Veröffentlicht in:Molecular immunology 2005-05, Vol.42 (8), p.979-985
Hauptverfasser: Demangel, Caroline, Zhou, Jie, Choo, Andre B.H., Shoebridge, Grant, Halliday, Gary M., Britton, Warwick J.
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container_end_page 985
container_issue 8
container_start_page 979
container_title Molecular immunology
container_volume 42
creator Demangel, Caroline
Zhou, Jie
Choo, Andre B.H.
Shoebridge, Grant
Halliday, Gary M.
Britton, Warwick J.
description 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. Immmunization 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.
doi_str_mv 10.1016/j.molimm.2004.09.034
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subjects Animals
Antigens, CD - immunology
Baculovirus
CD11c
CD11c Antigen - immunology
DEC-205
Dendritic cell
Dendritic Cells - immunology
Immunoglobulin Fragments - immunology
Langerhans Cells - immunology
Lectins, C-Type - immunology
Mice
Minor Histocompatibility Antigens
Receptors, Cell Surface - immunology
Single-chain antibody
Vaccine
title Single chain antibody fragments for the selective targeting of antigens to dendritic cells
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