Optimized vaccination regimen linked to exhaustive screening approaches identifies 2 novel HLA-B7 restricted epitopes within hepatitis C virus NS3 protein.
Broad immune responses, in particular specific for the NS3 protein and mediated by both CD8+ and CD4+T lymphocytes, are thought to play a critical role in the control of hepatitis C virus (HCV) infection. In this study, we searched for novel HLA-B*0702 NS3 restricted epitopes following an optimized NS3NS4 immunization protocol in transgenic mice expressing HLA-B*0702 molecule. Combining predicted and overlapping peptides, we identified two novel epitopes, WPA10 (aa 1111-1120) and LSP10 (aa 1153-1162), which triggered significant IFN-gamma-producing T cell frequencies and high CTL responses. Both epitopes were shown to be immunogenic when used as synthetic peptides to immunize mice. The relevance of these epitopes to humans was demonstrated, as both were able in vitro to recall specific IFN-gamma and IL10-producing cells from peripheral blood mononuclear cells of HCV infected patients. Such epitopes enlarge the pool of NS3-specific CD8+T cell epitopes available to perform immunomonitoring of HCV infection and to develop vaccines.
Martin
Perrine
P
IFR128 Biosciences Gerland, Lyon, France.
Parroche
Peggy
P
Pajot
Anthony
A
Chatel
Laurence
L
Barreto
Caroline
C
Touat
Leila
L
Dubois
Valérie
V
Rohrlich
Pierre-Simon
PS
Bain
Christine
C
Trépo
Christian
C
Negro
Francesco
F
Inchauspé
Geneviève
G
Fournillier
Anne
A
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017124:Conserved Sequence; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D015793:HLA-B7 Antigen; D016174:Hepacivirus / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014761:Viral Hepatitis Vaccines / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; D015793:HLA-B7 Antigen; D010446:Peptide Fragments; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C477444:HLA-B*07:02 antigen; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases