Vaccination against hepatitis C virus with dendritic cells transduced with an adenovirus encoding NS3 protein.
Chronic infection by hepatitis C virus (HCV) is characterized by the absence of efficient antiviral T-cell responses. Thus, vaccination strategies to induce strong anti-HCV T-cell responses are of paramount importance for prophylactic and therapeutic purposes. Dendritic cells (DCs) are the most potent antigen presenting cells; therefore, immunization with these cells loaded with viral antigens offers a new approach for induction of antiviral immunity. Here we show that immunization with DCs transfected with an adenovirus encoding non-structural 3 protein, from HCV (AdNS3), induced multiepitopic CD4 T helper cell 1 (Th1) and CD8 T-cell responses in different mouse strains. These responses prevented the growth of a tumorexpressing HCV proteins, in short- and long-term experiments. Moreover, immunization with AdNS3-transfected DCs did not induce anti-adenoviral antibodies, as compared to direct immunization with AdNS3, but elicited T-cell responses even in the presence of pre-existing anti-adenoviral antibodies. Finally, responses induced by this protocol down-regulated the expression of HCV RNA in the liver. In conclusion, DCs transfected with AdNS3 may prove to be an efficient anti-HCV vaccine.
Zabaleta
Aintzane
A
Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Llopiz
Diana
D
Arribillaga
Laura
L
Silva
Leyre
L
Riezu-Boj
José Ignacio
JI
Lasarte
Juan José
JJ
Borrás-Cuesta
Francisco
F
Prieto
Jesús
J
Sarobe
Pablo
P
D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation*; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
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