A vector-based minigene vaccine approach results in strong induction of T-cell responses specific of hepatitis C virus.
Multiepitope-based vaccines against hepatitis C virus (HCV) were designed in the form of three minigenes encompassing four domains of the NS3, NS4 and NS5B proteins that contain multiple class I/II restricted epitopes. The polyEp-WT minigene encodes all four domains in fusion, the polyEp-C minigene encodes the same fusion but optimised for mammalian translation and the polyEp-E3 minigene has an additional endoplasmic reticulum targeting sequence. Whereas the minigenes vectorised by DNA were poorly immunogenic, adenovirus vectorisation induced strong and broader IFNgamma-ELISpot and CTL responses in HLA-A2 transgenic mice. In addition, polyEp-WT and polyEp-E3 responses were found cross-reactive in a recombinant Listeria-NS3-based surrogate challenge. This study illustrates the potency of vectorised minigenes in the field of HCV vaccine development.
Martin
Perrine
P
TRANSGENE SA, Infectious Diseases Department, Site de l'AFSSA, 31 Avenue Tony Garnier, 69364 Lyon Cedex 07, France.
Simon
Benjamin
B
Lone
Yu-Chun
YC
Chatel
Laurence
L
Barry
Ronald
R
Inchauspé
Geneviève
G
Fournillier
Anne
A
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015169:Colony Count, Microbial; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008087:Listeria / Q000235:genetics / Q000254:growth & development; D008099:Liver / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D000939:Epitopes; D007371:Interferon-gamma; 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; C093542:NS4 protein, hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase