title: Vaccination with filamentous bacteriophages targeting DEC-205 induces DC maturation and potent anti-tumor T-cell responses in the absence of adjuvants.
abstract: The efficacy of a new vaccine-delivery vector, based on the filamentous bacteriophage fd displaying a single-chain antibody fragment known to bind the mouse DC surface molecule DEC-205, is reported. We demonstrate both in vitro and in vivo an enhanced receptor-mediated uptake of phage particles expressing the anti-DEC-205 fragment by DCs. We also report that DCs targeted by fd virions in the absence of other stimuli produce IFN-α and IL-6, and acquire a mature phenotype. Moreover, DC-targeting with fd particles double-displaying the anti-DEC-205 fragment on the pIII protein and the OVA(257-264)  antigenic determinant on the pVIII protein induced potent inhibition of the growth of the B16-OVA tumor in vivo. This protection was much stronger than other immunization strategies and similar to that induced by adoptively transferred DCs. Since targeting DEC-205 in the absence of DC activation/maturation agents has previously been described to result in tolerance, the ability of fd bacteriophages to induce a strong tumor-specific immune response by targeting DCs through DEC-205 is unexpected, and further validates the potential employment of this safe, versatile and inexpensive delivery system for vaccine formulation.
authors.affiliation: Institute of Protein Biochemistry, CNR, Naples, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Sartorius
authors.forename: Clotilde
authors.initials: C
authors.lastname: Bettua
authors.forename: Luciana
authors.initials: L
authors.lastname: D'Apice
authors.forename: Antonella
authors.initials: A
authors.lastname: Caivano
authors.forename: Maria
authors.initials: M
authors.lastname: Trovato
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.forename: Ivan
authors.initials: I
authors.lastname: Zanoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Granucci
authors.forename: Dina
authors.initials: D
authors.lastname: Mascolo
authors.forename: Pasquale
authors.initials: P
authors.lastname: Barba
authors.forename: Giovanna
authors.initials: G
authors.lastname: Del Pozzo
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: De Berardinis
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D019496:Cancer Vaccines; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004755:Enterobacteriaceae / Q000821:virology; D017912:Inovirus / Q000276:immunology* / Q000472:pathogenicity; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D058990:Molecular Targeted Therapy; D010047:Ovalbumin / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D047368:Tumor Burden; D014611:Vaccination; D014771:Virion / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: D015703:Antigens, CD; D019496:Cancer Vaccines; D036022:Capsid Proteins; C093569:DEC-205 receptor; D015850:Interleukin-6; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; C110366:OVA-8; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D057127:Single-Chain Antibodies; C119217:coat protein pVIII, Enterobacteria phage fd; D007371:Interferon-gamma; D010047:Ovalbumin