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...

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Bibliographic Details
Authors: 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
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
Description
Summary: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.

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