Vaccination with an adenoviral vector encoding hepatitis C virus (HCV) NS3 protein protects against infection with HCV-recombinant vaccinia virus.
Cellular immune response plays an important role in the clearance of hepatitis C virus (HCV). Thus, development of efficient ways to induce anti-viral cellular immune responses is an important step toward prevention and/or treatment of HCV infection. With this aim, we have constructed a replication-deficient recombinant adenovirus expressing HCV NS3 protein (RAdNS3). The efficacy of RAdNS3 was tested in vivo by measuring the protection against infection with a recombinant vaccinia virus expressing HCV-polyprotein (vHCV1-3011). Immunisation with 10(9)pfu of RAdNS3 induced anti-NS3 humoral, T helper and T cytotoxic responses. We identified eight epitopes recognised by IFN-gamma producing cells, five of them exhibiting lytic activity. Moreover, we show that RAdNS3 immunised mice were protected against challenge with vHCV1-3011 and that this protection was mediated by CD8(+) cells. In conclusion, our results suggest that adenoviral vectors encoding NS3 might be useful for the induction of prophylactic and/or therapeutic anti-HCV immunity.
Arribillaga
Laura
L
Department of Internal Medicine, Centro de Investigaciones Médicas Aplicadas (CIMA), University of Navarra, Pamplona, Spain. larribi@alumni.unav.es
de Cerio
Ascensión López Díaz
AL
Sarobe
Pablo
P
Casares
Noelia
N
Gorraiz
Marta
M
Vales
Africa
A
Bruna-Romero
Oscar
O
Borrás-Cuesta
Francisco
F
Paranhos-Baccala
Glaucia
G
Prieto
Jesús
J
Ruiz
Juan
J
Lasarte
Juan José
JJ
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000517:prevention & control*; D018937:Hepatitis C Antibodies / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D018937:Hepatitis C Antibodies; D014614:Vaccines, Synthetic; 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