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PMID: 10618412 Published · ppublish English Journal Article Retracted Publication

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.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 1 ·2000-01-04 ·Pages 297-302

Arichi T, Saito T, Major ME, Belyakov IM, Shirai M, Engelhard VH, Feinstone SM, Berzofsky JA

Abstract

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.

MeSH Terms
Animals Antibodies, Monoclonal/immunology CD8-Positive T-Lymphocytes/immunology Cytotoxicity Tests, Immunologic Female HLA-A2 Antigen/immunology Hepacivirus/genetics,immunology Hepatitis, Animal/immunology Humans Mice Mice, Transgenic Nucleocapsid/genetics,immunology Ovary/immunology T-Lymphocytes, Cytotoxic/immunology Vaccines, DNA/immunology Vaccinia/genetics
Chemicals
Antibodies, Monoclonal HLA-A2 Antigen Vaccines, DNA
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Arichi T
Molecular Immunogenetics, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Saito T
Major M E
Belyakov I M
Shirai M
Engelhard V H
Feinstone S M
Berzofsky J A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.97.1.297
Published
2000-01-04
Pages
297-302
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC26657
Subset
IM
Corrections
RetractionIn
PMID: 11331781
CommentIn
PMID: 12449910
External Links
PubMed source DOI: 10.1073/pnas.97.1.297 PMC Full Text View journal details
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