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. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sartorius, R., Bettua, C., D'Apice, L., Caivano, A., Trovato, M., Russo, D., et al. (2011). Vaccination with filamentous bacteriophages targeting DEC-205 induces DC maturation and potent anti-tumor T-cell responses in the absence of adjuvants. EUROPEAN JOURNAL OF IMMUNOLOGY, 41(9), 2573-2584 [10.1002/eji.201141526].

Vaccination with filamentous bacteriophages targeting DEC-205 induces DC maturation and potent anti-tumor T-cell responses in the absence of adjuvants

ZANONI, IVAN;GRANUCCI, FRANCESCA;
2011

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. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Articolo in rivista - Articolo scientifico
CD8 + T cells; DEC-205; Dendritic cells; Filamentous bacteriophage fd; Vaccination; Animals; Antigens, CD; Capsid Proteins; Cell Differentiation; Dendritic Cells; Enterobacteriaceae; Inovirus; Interferon-gamma; Interleukin-6; Lectins, C-Type; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Molecular Targeted Therapy; Ovalbumin; Peptide Fragments; Receptors, Cell Surface; Single-Chain Antibodies; Transgenes; Tumor Burden; Vaccination; Virion; Cancer Vaccines; Immunology; Immunology and Allergy
English
2011
41
9
2573
2584
none
Sartorius, R., Bettua, C., D'Apice, L., Caivano, A., Trovato, M., Russo, D., et al. (2011). Vaccination with filamentous bacteriophages targeting DEC-205 induces DC maturation and potent anti-tumor T-cell responses in the absence of adjuvants. EUROPEAN JOURNAL OF IMMUNOLOGY, 41(9), 2573-2584 [10.1002/eji.201141526].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/68544
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