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.
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.
Maguire
Casey A
CA
Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Sapinoro
Ramil
R
Girgis
Natasha
N
Rodriguez-Colon
Sol M
SM
Ramirez
Servio H
SH
Williams
Jennifer
J
Dewhurst
Stephen
S
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
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