An accelerated vaccine schedule with a poly-antigenic hepatitis C virus MVA-based candidate vaccine induces potent, long lasting and in vivo cross-reactive T cell responses.
We designed and evaluated in HLA-class I transgenic mouse models a hepatitis C virus (HCV) T cell-based MVA vectored vaccine expressing three viral antigens known to be targets of potent CD8+- and CD4+-mediated responses. An accelerated (3 week-based) vaccination induced specific CD8+ T cells harboring two effector functions (cytolytic activity - both in vitro and in vivo- and production of IFNgamma) as well as specific CD4+ T cells recognizing all three vaccine antigens. Responses were long lasting (6 months), boostable by a fourth MVA vaccination and in vivo cross-reactive as demonstrated in a surrogate Listeria-based challenge assay. This candidate vaccine has now moved into clinical trials.
Fournillier
A
A
Transgene S.A., Site AFSSA, 31 avenue Tony Garnier, 69364 Lyon Cédex 07, France. fournillier@transgene.fr
Gerossier
E
E
Evlashev
A
A
Schmitt
D
D
Simon
B
B
Chatel
L
L
Martin
P
P
Silvestre
N
N
Balloul
J M
JM
Barry
R
R
Inchauspé
G
G
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000235:genetics; D015793:HLA-B7 Antigen / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000235:genetics; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D015789:HLA-A2 Antigen; D015793:HLA-B7 Antigen; D018936:Hepatitis C Antigens; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines