Open AccessAntigen delivery by filamentous bacteriophage fd displaying an anti‐ DEC ‐205 single‐chain variable fragment confers adjuvanticity by triggering a TLR 9‐mediated immune response
Author(s) -
Sartorius Rossella,
D'Apice Luciana,
Trovato Maria,
Cuccaro Fausta,
Costa Valerio,
De Leo Maria Giovanna,
Marzullo Vincenzo Manuel,
Biondo Carmelo,
D'Auria Sabato,
De Matteis Maria Antonietta,
Ciccodicola Alfredo,
De Berardinis Piergiuseppe
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201404525
Subject(s) - bacteriophage , immune system , antigen , microbiology and biotechnology , fragment (logic) , chemistry , single chain variable fragment , biology , immunology , antibody , gene , biochemistry , computer science , escherichia coli , monoclonal antibody , programming language
Filamentous bacteriophage fd particles delivering antigenic determinants via DEC ‐205 (fdsc‐α DEC ) represent a powerful delivery system that induces CD 8 + 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‐α DEC was MYD 88 mediated and TLR 9 dependent. We also found that fdsc‐α DEC is delivered into LAMP ‐1‐positive compartments and co‐localizes with TLR 9. 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 TLR 9 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.