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首页> 外文期刊>Vaccine >Recombinant ovine atadenovirus induces a strong and sustained T cell response against the hepatitis C virus NS3 antigen in mice
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Recombinant ovine atadenovirus induces a strong and sustained T cell response against the hepatitis C virus NS3 antigen in mice

机译：重组羊腺病毒在小鼠中诱导针对丙型肝炎病毒NS3抗原的强而持续的T细胞反应

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摘要

Ovine atadenovirus (OAdV) is a novel gene transfer vector with excellent in vivo gene transfer characteristics. In the present study, we have investigated the ability of an OAdV vector to mediate a T cell response to an antigen of the hepatitis C virus (HCV) in mice. Specifically, an expression cassette coding for non-structural protein 3 (NS3) of hepatitis C virus was inserted into the OAdV genome and the resulting recombinant virus (OAdV-ns3) was shown to propagate stably and to express the ns3 gene at a high level in vitro. A single injection of this non-replicating vector into BALB/c mice resulted in a strong induction of NS3-specific, IFN-gamma secreting T-lymphocytes as measured by direct ex vivo ELISpot assay. The number of IFN-gamma secreting lymphocytes remained nearly unaltered for a period of at least 10 weeks. The immune response was shown to depend on virus dose but a single intramuscular injection of less than 10(8) infectious particles of OAdV-ns3 was sufficient to induce a significant NS3-specific T cell response. Moreover, this response was not affected by prior immunisation of animals with human adenovirus type 5 (HAdV-5). The results of our study provide proof for the concept that OAdV vectors may be valuable tools for vaccination and immunotherapy even in the face of natural immunity to human adenoviruses.
机译：绵羊腺病毒（OAdV）是一种新型的基因转移载体，具有出色的体内基因转移特性。在本研究中，我们已经研究了OAdV载体介导小鼠T细胞对丙型肝炎病毒（HCV）抗原反应的能力。具体地，将编码丙型肝炎病毒的非结构蛋白3（NS3）的表达盒插入OAdV基因组，结果显示重组病毒（OAdV-ns3）稳定繁殖并高水平表达ns3基因。体外。通过直接离体ELISpot分析测定，将这种非复制型载体单次注射到BALB / c小鼠中可强烈诱导NS3特异性，分泌IFN-γ的T淋巴细胞。在至少10周的时间内，IFN-γ分泌淋巴细胞的数量几乎保持不变。免疫反应显示取决于病毒剂量，但是一次肌内注射OAdV-ns3小于10（8）感染性颗粒足以诱导显着的NS3特异性T细胞反应。此外，该反应不受事先用5型人腺病毒（HAdV-5）免疫的动物的影响。我们的研究结果为以下概念提供了证明：即使面对人类腺病毒具有天然免疫力，OAdV载体也可能是用于疫苗接种和免疫疗法的有价值的工具。

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