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Modeling of the transfer of adoptive immunity to hepatitis B and C virus in liver transplantation

肝移植中乙型和丙型肝炎病毒过继免疫转移的建模

基本信息

批准号：
61355772
负责人：
Dr. Melanie Fiedler
金额：
--
依托单位：
Institut für Virologie
依托单位国家：
德国
项目类别：
Clinical Research Units
财政年份：
2008
资助国家：
德国
起止时间：
2007-12-31 至 2010-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/61355772?language=en
关键词：
Modeling transfer adoptive immunity hepatitis

项目摘要

During the first funding period, our group has demonstrated the principal possibility of a transfer of cellular and humoral HBV-specific immunity by liver transplantation after immunization of donors with a highly immunogenic HBV vaccine. In the current study, this investigation will be extended by inclusion of a larger number of patients. A more difficult situation is observed in the research activities directed at the prevention of HCV reinfection of liver-transplanted patients. The resolution of HCV infection was found to be strongly associated with vigorous cell mediated immune responses to NS3 and NS5. Virus-neutralizing antibodies might also play a role in the clearance of HCV. The primary aim of this project is the development of a prototype HCV vaccine, which in perspective may be used for immunization of donors in order to prevent reinfection of the transplanted liver with HCV. To this end, we intend to use virus-like particles (VLPs) based on HBV nucleocapsid as a carrier of the fragments of HCV proteins NS3, NS5, and E2, bearing Th and B-cell epitopes. These chimeric recombinant VLPs should induce HCV-specific cellular and humoral immune responses. The prepared VLPs will be used for immunization in mice. The best chimeric VLPs will subsequently be used in experiments on transfer of adoptive immunity to HCV by liver transplantation in rats. These preclinical model experiments will evaluate the principal feasibility of the adoptive transfer scheme for HCV by liver transplantation.

在第一个资助期，我们的小组已经证明了在供者接种高免疫原性的乙肝疫苗后，通过肝移植转移细胞和体液乙肝特异性免疫的主要可能性。在目前的研究中，这项调查将通过纳入更多的患者来扩大。在针对预防肝移植患者丙型肝炎病毒再感染的研究活动中，观察到了更困难的情况。丙型肝炎病毒感染的解决与对NS3和NS5的强有力的细胞免疫反应密切相关。病毒中和抗体也可能在清除丙型肝炎病毒方面发挥作用。该项目的主要目标是开发一种原型丙型肝炎病毒疫苗，从前景来看，该疫苗可用于对捐赠者进行免疫，以防止移植肝脏再次感染丙型肝炎病毒。为此，我们打算使用基于病毒核衣壳的病毒样颗粒(VLP)作为携带带有Th和B细胞表位的丙型肝炎病毒蛋白NS3、NS5和E2片段的载体。这些嵌合的重组VLP可以诱导丙型肝炎病毒特异性的细胞和体液免疫应答。制备的VLP将用于小鼠的免疫。最好的嵌合VLP随后将用于通过大鼠肝移植将过继免疫转移到丙型肝炎病毒的实验中。这些临床前模型实验将评估丙型肝炎病毒肝移植过继转移方案的基本可行性。