title: Induction of antigen-specific immune responses in vivo after vaccination with dendritic cells transduced with adenoviral vectors encoding hepatitis C virus NS3.
abstract: Dendritic cells (DC) are potent antigen-presenting cells that play a critical role in the initiation of immunity to viral infections. Direct transduction of DC appears to be the major pathway in vivo responsible for induction of antigen specific immune responses. The aim of this study was to explore the vaccine potential of DC transduced with adenoviral vectors encoding the HCV nonstructural protein 3 (AdNS3) compared to DC pulsed with recombinant NS3 (rNS3). Mice (Balb/c and C57BL/6 transgenic for HLA-A2.1) were immunized with DC based vaccines. After the immunization, antigen specific immune responses including humoral responses, cytokine secretion, and IFN-gamma-producing T cell responses were analyzed. In both strains of mice inoculated with DC transduced with an adenovirus, the generated NS3 specific antibody response and IFN-gamma-secreting T cell response were stronger than that generated by rNS3-pulsed DC. Analysis of the cytokine profiles revealed that immunization with AdNS3 transduced DC shifted the antigen specific immunity towards Th1 responses. DC transduced with AdNS3 are superior to DC pulsed with rNS3 in inducing vigorous humoral and Th1-type cellular responses against NS3. The results demonstrate for the first time the immunogenic potential of genetically modified DC by a prime and boost approach in eliciting a strong NS3-specific, cell-mediated, humoral immune response in both Balb/c mice and HLA-A2.1 transgenic mice.
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg, Heidelberg, Germany.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiang
authors.forename: Christoph
authors.initials: C
authors.lastname: Eisenbach
authors.forename: Catalin Mario
authors.initials: CM
authors.lastname: Lupu
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ernst
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.forename: Jens
authors.initials: J
authors.lastname: Encke
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000918:Antibody Specificity; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation* / Q000821:virology; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000235:genetics; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000517:prevention & control; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014161:Transduction, Genetic; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D015789:HLA-A2 Antigen; D018937:Hepatitis C Antibodies; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases