Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCV-specific cytotoxic T lymphocyte induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model.
DNA vaccines express antigens intracellularly and effectively induce cellular immune responses. Because only chimpanzees can be used to model human hepatitis C virus (HCV) infections, we developed a small-animal model using HLA-A2.1-transgenic mice to test induction of HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs) and protection against recombinant vaccinia expressing HCV-core. A plasmid encoding the HCV-core antigen induced CD8(+) CTLs specific for three conserved endogenously expressed core peptides presented by human HLA-A2.1. When challenged, DNA-immunized mice showed a substantial (5-12 log(10)) reduction in vaccinia virus titer compared with mock-immunized controls. This protection, lasting at least 14 mo, was shown to be mediated by CD8(+) cells. Thus, a DNA vaccine expressing HCV-core is a potential candidate for a prophylactic vaccine for HLA-A2.1(+) humans.
Arichi
T
T
Molecular Immunogenetics, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Saito
T
T
Major
M E
ME
Belyakov
I M
IM
Shirai
M
M
Engelhard
V H
VH
Feinstone
S M
SM
Berzofsky
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006520:Hepatitis, Animal / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D019251:Nucleocapsid / Q000235:genetics / Q000276:immunology; D010053:Ovary / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D014615:Vaccinia / Q000235:genetics*
D000911:Antibodies, Monoclonal; D015789:HLA-A2 Antigen; D019444:Vaccines, DNA