Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response

EMBO Mol Med. 2015 Apr 17;7(7):973-88. doi: 10.15252/emmm.201404525. Print 2015 Jul.


Filamentous bacteriophage fd particles delivering antigenic determinants via DEC-205 (fdsc-αDEC) represent a powerful delivery system that induces CD8(+) T-cell responses even when administered in the absence of adjuvants or maturation stimuli for dendritic cells. In order to investigate the mechanisms of this activity, RNA-Sequencing of fd-pulsed dendritic cells was performed. A significant differential expression of genes involved in innate immunity, co-stimulation and cytokine production was observed. In agreement with these findings, we demonstrate that induction of proinflammatory cytokines and type I interferon by fdsc-αDEC was MYD88 mediated and TLR9 dependent. We also found that fdsc-αDEC is delivered into LAMP-1-positive compartments and co-localizes with TLR9. Thus, phage particles containing a single-strand DNA genome rich in CpG motifs delivered via DEC-205 are able to intercept and trigger the active TLR9 innate immune receptor into late endosome/lysosomes and to enhance the immunogenicity of the displayed antigenic determinants. These findings make fd bacteriophage a valuable tool for immunization without administering exogenous adjuvants.

Keywords: DEC‐205; TLR9; antigen delivery; dendritic cells; filamentous bacteriophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / metabolism*
  • Animals
  • Antigens / immunology*
  • Antigens / metabolism
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Surface Display Techniques
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Drug Carriers
  • Gene Expression Profiling
  • Immunity, Innate
  • Inovirus / genetics*
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism*
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Single-Chain Antibodies / immunology
  • Single-Chain Antibodies / metabolism*
  • Toll-Like Receptor 9 / metabolism*


  • Adjuvants, Immunologic
  • Antigens
  • Antigens, CD
  • DEC-205 receptor
  • Drug Carriers
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Receptors, Cell Surface
  • Single-Chain Antibodies
  • TLR9 protein, human
  • Toll-Like Receptor 9