Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus
A replication-defective recombinant adenovirus (RAd), RAdCMV-CE1, containing core and E1 genes of hepatitis C virus (HCV) was constructed. RAdCMV-CE1 was able to express core and E1 proteins both in mice and human cells. Immunization of BALB/c mice with RAdCMV-CE1 induced a specific cytotoxic T-cell...
| Authors: | ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 1997 |
| Country: | España |
| Institution: | Universidad de Navarra |
| Repository: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Language: | English |
| OAI Identifier: | oai:dadun.unav.edu:10171/21662 |
| Online Access: | https://hdl.handle.net/10171/21662 |
| Access Level: | Open access |
| Keyword: | Defective Viruses/immunology Hepacivirus/immunology T-Lymphocytes, Cytotoxic/immunology Viral Core Proteins/immunology Viral Envelope Proteins/immunology |
| _version_ | 1878739618201862144 |
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| author | Bruña-Romero, O. (Oscar)|||/items/a10bef04-a282-4ea4-a58e-7b570690c04f |
| author2 | Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c Wilkinson, G. (Gavin)|||/items/ff263d1b-b59c-4dfd-9696-ad75c56803ed Grace, K. (Ken)|||/items/c37e648b-dc8c-44b0-a2dd-54e40106f0ec Klarke, B. (Berwyn)|||/items/ca3574c1-0a97-4cd4-91d0-f0752dc4931b Borras-Cuesta, F. (Francisco)|||/items/9f3719bd-4cf6-4e5b-b672-39179b54e8cc Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 |
| author2_role | author author author author author author |
| author_browse | Borras-Cuesta, F. (Francisco)|||/items/9f3719bd-4cf6-4e5b-b672-39179b54e8cc Bruña-Romero, O. (Oscar)|||/items/a10bef04-a282-4ea4-a58e-7b570690c04f Grace, K. (Ken)|||/items/c37e648b-dc8c-44b0-a2dd-54e40106f0ec Klarke, B. (Berwyn)|||/items/ca3574c1-0a97-4cd4-91d0-f0752dc4931b Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Wilkinson, G. (Gavin)|||/items/ff263d1b-b59c-4dfd-9696-ad75c56803ed |
| author_facet | Bruña-Romero, O. (Oscar)|||/items/a10bef04-a282-4ea4-a58e-7b570690c04f Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c Wilkinson, G. (Gavin)|||/items/ff263d1b-b59c-4dfd-9696-ad75c56803ed Grace, K. (Ken)|||/items/c37e648b-dc8c-44b0-a2dd-54e40106f0ec Klarke, B. (Berwyn)|||/items/ca3574c1-0a97-4cd4-91d0-f0752dc4931b Borras-Cuesta, F. (Francisco)|||/items/9f3719bd-4cf6-4e5b-b672-39179b54e8cc Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 |
| author_role | author |
| collection | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| description | A replication-defective recombinant adenovirus (RAd), RAdCMV-CE1, containing core and E1 genes of hepatitis C virus (HCV) was constructed. RAdCMV-CE1 was able to express core and E1 proteins both in mice and human cells. Immunization of BALB/c mice with RAdCMV-CE1 induced a specific cytotoxic T-cell response against the two HCV proteins. This response was characterized using a panel of 60 synthetic 14- or 15-mer overlapping peptides (10 amino-acid overlap) spanning the entire sequence of these proteins. Five main epitopes were found in the core protein, four of which had been previously described either in mice or humans. One single novel epitope was found in E1. Fine mapping of this E1 determinant, showed that octamer GHRMAWDM is the minimal epitope recognized by cytotoxic T lymphocytes (CTL). The cytotoxic T-cell response was H-2d restricted, lasted for at least 100 days, and was mediated by T cells with the classic CD4-CD8+ phenotype. This work demonstrates that replication-defective recombinant adenoviruses can efficiently express HCV proteins and are able to induce an in vivo cytotoxic T-cell response against a diversity of epitopes from HCV antigens. These vectors should be taken into consideration in the design of vaccines and also as a means to stimulate specific T-cell responses in chronic HCV carriers. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_c4dd22245fe7e619462d00a441fdb76d |
| institution | Universidad de Navarra |
| instname_str | Universidad de Navarra |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:dadun.unav.edu:10171/21662 |
| publishDate | 1997 |
| publishDateSort | 1997 |
| publisher | Wiley-Blackwell |
| publisherStr | Wiley-Blackwell |
| reponame_str | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| spelling | Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus Bruña-Romero, O. (Oscar)|||/items/a10bef04-a282-4ea4-a58e-7b570690c04f Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c Wilkinson, G. (Gavin)|||/items/ff263d1b-b59c-4dfd-9696-ad75c56803ed Grace, K. (Ken)|||/items/c37e648b-dc8c-44b0-a2dd-54e40106f0ec Klarke, B. (Berwyn)|||/items/ca3574c1-0a97-4cd4-91d0-f0752dc4931b Borras-Cuesta, F. (Francisco)|||/items/9f3719bd-4cf6-4e5b-b672-39179b54e8cc Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Defective Viruses/immunology Hepacivirus/immunology T-Lymphocytes, Cytotoxic/immunology Viral Core Proteins/immunology Viral Envelope Proteins/immunology A replication-defective recombinant adenovirus (RAd), RAdCMV-CE1, containing core and E1 genes of hepatitis C virus (HCV) was constructed. RAdCMV-CE1 was able to express core and E1 proteins both in mice and human cells. Immunization of BALB/c mice with RAdCMV-CE1 induced a specific cytotoxic T-cell response against the two HCV proteins. This response was characterized using a panel of 60 synthetic 14- or 15-mer overlapping peptides (10 amino-acid overlap) spanning the entire sequence of these proteins. Five main epitopes were found in the core protein, four of which had been previously described either in mice or humans. One single novel epitope was found in E1. Fine mapping of this E1 determinant, showed that octamer GHRMAWDM is the minimal epitope recognized by cytotoxic T lymphocytes (CTL). The cytotoxic T-cell response was H-2d restricted, lasted for at least 100 days, and was mediated by T cells with the classic CD4-CD8+ phenotype. This work demonstrates that replication-defective recombinant adenoviruses can efficiently express HCV proteins and are able to induce an in vivo cytotoxic T-cell response against a diversity of epitopes from HCV antigens. These vectors should be taken into consideration in the design of vaccines and also as a means to stimulate specific T-cell responses in chronic HCV carriers. Wiley-Blackwell https://hdl.handle.net/10171/21662 |
| spellingShingle | Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus Bruña-Romero, O. (Oscar)|||/items/a10bef04-a282-4ea4-a58e-7b570690c04f Defective Viruses/immunology Hepacivirus/immunology T-Lymphocytes, Cytotoxic/immunology Viral Core Proteins/immunology Viral Envelope Proteins/immunology |
| title | Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus |
| title_full | Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus |
| title_fullStr | Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus |
| title_full_unstemmed | Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus |
| title_short | Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus |
| title_sort | Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus |
| topic | Defective Viruses/immunology Hepacivirus/immunology T-Lymphocytes, Cytotoxic/immunology Viral Core Proteins/immunology Viral Envelope Proteins/immunology |
| topic_facet | Defective Viruses/immunology Hepacivirus/immunology T-Lymphocytes, Cytotoxic/immunology Viral Core Proteins/immunology Viral Envelope Proteins/immunology |
| url | https://hdl.handle.net/10171/21662 |