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...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2000-01, Vol.97 (1), p.297-302 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Arichi, Tatsumi Saito, Takafumi Major, Marian E. Belyakov, Igor M. Shirai, Mutsunori Engelhard, Victor H. Feinstone, Stephen M. Berzofsky, Jay A. |
| description | 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 (5-12log10) 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. |
| doi_str_mv | 10.1073/pnas.97.1.297 |
| format | Article |
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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 (5-12log10) 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. 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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 (5-12log10) 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.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Biological Sciences</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cytotoxicity Tests, Immunologic</subject><subject>DNA vaccines</subject><subject>Epitopes</subject><subject>Female</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - immunology</subject><subject>hepatitis C virus</subject><subject>Hepatitis, Animal - immunology</subject><subject>histocompatibility antigen HLA</subject><subject>HLA-A2 Antigen - immunology</subject><subject>Humans</subject><subject>Immunization</subject><subject>Infections</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecules</subject><subject>Nucleocapsid - genetics</subject><subject>Nucleocapsid - immunology</subject><subject>Ovary - immunology</subject><subject>Spleen cells</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Vaccination</subject><subject>Vaccines, DNA - immunology</subject><subject>Vaccinia - genetics</subject><subject>Viruses</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kkuP0zAUhSMEYsrAkhUIeQOCRYJfsRPEpgqPjlQegtJt5Dr21KPEDraDJn-RX4WZlhnYsPFD5zv32Lo3yx4iWCDIycvRilDUvEAFrvmtbIFgjXJGa3g7W0CIeV5RTE-yeyFcQAjrsoJ3sxMEGaoowovs52fvxv3cCxmNBG8-LsFWSGmsAtp5sFKjiCaaABqwNX4K4Pmq2b4AZ1arZHD2FUj3_OuopNHJ38zRRXeZThuwnodx7-QcVcK76QoHwnYgJcaDG2jvhqsKX5R0w85YYePxAUbcpADz2wlW62W-xAUCGy9sOFc25XxwU1Bp7VR_P7ujRR_Ug-N-mn1793bTrPL1p_dnzXKdSwpZzBXvhKg44UxKzTpcMaY5qwnSuKtoRSRFUGIikNKEl3hHeUdZCRPVQYJISU6z14e647QbVCeVjV707ejNIPzcOmHafxVr9u25-9Fixkqe7M-Odu--TyrEdjBBqr4XVqXPtIjT1BmMEvjk75zrgD_NS8DjI5Bm4FqueYvaNAtJfvofudVT30d1GRP36MBdhOj8TQxGvKLkF74mva8</recordid><startdate>20000104</startdate><enddate>20000104</enddate><creator>Arichi, Tatsumi</creator><creator>Saito, Takafumi</creator><creator>Major, Marian E.</creator><creator>Belyakov, Igor M.</creator><creator>Shirai, Mutsunori</creator><creator>Engelhard, Victor H.</creator><creator>Feinstone, Stephen M.</creator><creator>Berzofsky, Jay A.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>The National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QO</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20000104</creationdate><title>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</title><author>Arichi, Tatsumi ; 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| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2000-01, Vol.97 (1), p.297-302 |
| issn | 0027-8424 1091-6490 |
| language | eng |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Antibodies Antibodies, Monoclonal - immunology Biological Sciences CD8-Positive T-Lymphocytes - immunology Cytotoxicity Tests, Immunologic DNA vaccines Epitopes Female Hepacivirus - genetics Hepacivirus - immunology hepatitis C virus Hepatitis, Animal - immunology histocompatibility antigen HLA HLA-A2 Antigen - immunology Humans Immunization Infections Mice Mice, Transgenic Molecules Nucleocapsid - genetics Nucleocapsid - immunology Ovary - immunology Spleen cells T lymphocytes T-Lymphocytes, Cytotoxic - immunology Vaccination Vaccines, DNA - immunology Vaccinia - genetics Viruses |
| title | 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 |
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