Primary and memory T cell responses induced by hepatitis C virus multiepitope long peptides.
To develop a vaccine against hepatitis C virus, we synthesized four long peptides from nonstructural proteins NS3, NS4 and NS5B containing HLA-class I and class II epitopes mainly inducing responses in natural infection. In HLA-A2.1 transgenic mice, the four peptides primed higher CTL responses to 6:7 minimal HLA-A2 epitopes than those induced by the minimal epitopes. HLA-A2.1/HLA-DR1 transgenic mice immunized with one peptide, containing a class II epitope implicated in viral resolution, developed IFNgamma-producing CD4+-T and CD8+-T cells. These peptides recalled HCV-specific IFNgamma-producing cells from HCV-infected patients' PBMC. This support the selection of these domains for inclusion in a vaccine formulation.
Fournillier
A
A
FRE 2736 CNRS/bioMérieux, IFR 128 BioSciences Lyon-Gerland, 46 Allée d'Italie, 69364 Lyon cedex 07, France. Anna.Fournillier@ens-lyon.fr
Dupeyrot
P
P
Martin
P
P
Parroche
P
P
Pajot
A
A
Chatel
L
L
Fatmi
A
A
Gerossier
E
E
Bain
C
C
Lone
Y C
YC
Trépo
C
C
Inchauspé
G
G
D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics; D015798:HLA-DR1 Antigen / Q000235:genetics; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / 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; D012324:RNA-Dependent RNA Polymerase
D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015798:HLA-DR1 Antigen; D007371:Interferon-gamma; D011994:Recombinant Proteins; 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