Stimulation of Innate and Adaptive Immunity by Using Filamentous Bacteriophage fd Targeted to DEC-205

The filamentous bacteriophage fd, codisplaying antigenic determinants and a single chain antibody fragment directed against the dendritic cell receptor DEC-205, is a promising vaccine candidate for its safety and its ability to elicit innate and adaptive immune response in absence of adjuvants. By using a system vaccinology approach based on RNA-Sequencing (RNA-Seq) analysis, we describe a relevant gene modulation in dendritic cells pulsed with anti-DEC-205 bacteriophages fd. RNA-Seq data analysis indicates that the bacteriophage fd virions are sensed as a pathogen by dendritic cells; they activate the danger receptors that trigger an innate immune response and thus confer a strong adjuvanticity that is needed to obtain a long-lasting adaptive immune response.

[1]  G. Cortese,et al.  The Use of Filamentous Bacteriophage fd to Deliver MAGE-A10 or MAGE-A3 HLA-A2-Restricted Peptides and to Induce Strong Antitumor CTL Responses1 , 2008, The Journal of Immunology.

[2]  Simon Yu,et al.  INTERFEROME v2.0: an updated database of annotated interferon-regulated genes , 2012, Nucleic Acids Res..

[3]  Donatella Scotto di Mase,et al.  Comparative analysis of new innovative vaccine formulations based on the use of procaryotic display systems. , 2007, Vaccine.

[4]  O. Beretta,et al.  Dendritic cells in pathogen recognition and induction of immune responses: a functional genomics approach , 2006, Journal of leukocyte biology.

[5]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[6]  D. Marvin,et al.  Structure and assembly of filamentous bacteriophages. , 2014, Progress in biophysics and molecular biology.

[7]  M. Campbell,et al.  PANTHER: a library of protein families and subfamilies indexed by function. , 2003, Genome research.

[8]  J. Oviedo-Boyso,et al.  Collaborative Action of Toll-Like and Nod-Like Receptors as Modulators of the Inflammatory Response to Pathogenic Bacteria , 2014, Mediators of inflammation.

[9]  A. Ciccodicola,et al.  Massive-Scale RNA-Seq Analysis of Non Ribosomal Transcriptome in Human Trisomy 21 , 2011, PloS one.

[10]  R. Steinman,et al.  The Dendritic Cell Receptor for Endocytosis, Dec-205, Can Recycle and Enhance Antigen Presentation via Major Histocompatibility Complex Class II–Positive Lysosomal Compartments , 2000, The Journal of cell biology.

[11]  K. Fitzgerald,et al.  Innate immune sensing of DNA viruses. , 2011, Virology.

[12]  J. Guardiola,et al.  Recognition of HIV-derived B and T cell epitopes displayed on filamentous phages. , 1999, Vaccine.

[13]  R. Perham,et al.  Immunological properties of foreign peptides in multiple display on a filamentous bacteriophage. , 1993, Gene.

[14]  David G Hendrickson,et al.  Differential analysis of gene regulation at transcript resolution with RNA-seq , 2012, Nature Biotechnology.

[15]  S. Bhattacharjee,et al.  CXCL10 Is Critical for the Generation of Protective CD8 T Cell Response Induced by Antigen Pulsed CpG-ODN Activated Dendritic Cells , 2012, PloS one.

[16]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[17]  Cole Trapnell,et al.  TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions , 2013, Genome Biology.

[18]  E. Borden,et al.  Proteomic identification of proteins conjugated to ISG15 in mouse and human cells. , 2005, Biochemical and biophysical research communications.

[19]  T. Lawrence,et al.  Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming , 2014, The EMBO journal.

[20]  G F Pierce,et al.  Gene transfer to mammalian cells using genetically targeted filamentous bacteriophage , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[21]  F. Granucci,et al.  Vaccination with filamentous bacteriophages targeting DEC‐205 induces DC maturation and potent anti‐tumor T‐cell responses in the absence of adjuvants , 2011, European journal of immunology.

[22]  J. Guardiola,et al.  Phage display of peptide epitopes from HIV-1 elicits strong cytolytic responses , 2000, Nature Biotechnology.

[23]  O. Beretta,et al.  Gene Expression Profiles Identify Inflammatory Signatures in Dendritic Cells , 2010, PloS one.

[24]  A. García-Sastre,et al.  HERC6 Is the Main E3 Ligase for Global ISG15 Conjugation in Mouse Cells , 2012, PloS one.

[25]  Ming Yan,et al.  Protein ISGylation modulates the JAK-STAT signaling pathway. , 2003, Genes & development.

[26]  C. Mandl,et al.  Vaccines for the twenty-first century society , 2011, Nature Reviews Immunology.

[27]  M. Pabst,et al.  Removal of endotoxin from protein solutions by phase separation using Triton X-114. , 1990, Journal of immunological methods.

[28]  Bali Pulendran,et al.  Immunological mechanisms of vaccination , 2011, Nature Immunology.