title: Recombinant adenovirus type 5 vectors that target DC-SIGN, ChemR23 and alpha(v)beta3 integrin efficiently transduce human dendritic cells and enhance presentation of vectored antigens.
abstract: Recombinant adenoviruses (rAds) represent a promising system for vaccine delivery but transduce dendritic cells (DC) relatively poorly. To address this concern, we used a biotin-avidin linkage to conjugate rAd vectors to ligands which bind with high affinity to selected receptors on DC (ChemR23, alpha(v)beta3 integrin, and DC-SIGN). The targeted vectors had an enhanced ability to transduce human monocyte-derived DC compared to untargeted virus. In addition, DC transduced with targeted rAd vectors were more efficient at stimulating cytokine production by autologous memory CD8+ T cells, against a vector-encoded antigen. These results expand the range of cell surface receptors that can be used to target rAd5 vectors to DC, and may facilitate future development of rAd-based vaccines.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Casey A
authors.initials: CA
authors.lastname: Maguire
authors.forename: Ramil
authors.initials: R
authors.lastname: Sapinoro
authors.forename: Natasha
authors.initials: N
authors.lastname: Girgis
authors.forename: Sol M
authors.initials: SM
authors.lastname: Rodriguez-Colon
authors.forename: Servio H
authors.initials: SH
authors.lastname: Ramirez
authors.forename: Jennifer
authors.initials: J
authors.lastname: Williams
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017951:Antigen Presentation / Q000235:genetics*; D000941:Antigens / Q000235:genetics*; D001710:Biotin; D016827:CD8 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007114:Immunization; D039302:Integrin alphaVbeta3 / Q000235:genetics*; D037181:Lectins, C-Type / Q000235:genetics*; D008024:Ligands; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D050863:Synaptotagmin I / Q000235:genetics; D014161:Transduction, Genetic; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000941:Antigens; D001710:Biotin; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D049452:Green Fluorescent Proteins; D039302:Integrin alphaVbeta3; D037181:Lectins, C-Type; D008024:Ligands; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D050863:Synaptotagmin I; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C102741:CMKLR1 protein, human