Journal
MOLECULAR IMMUNOLOGY
Volume 42, Issue 8, Pages 979-985Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2004.09.034
Keywords
dendritic cell; DEC-205; CD11c; single-chain antibody; vaccine
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In order to target antigens (Ags) selectively to dendritic cells (DC), we derived single chain antibody fragments (scFvs) from NLDC145 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 Immoral and cellular compartments, in contrast to DNA vaccines expressing scN418-targeted or untargeted antigen. Out- 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. (c) 2004 Elsevier Ltd. All rights reserved.
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