Studies of hepatitis C virus in chimpanzees and their importance for vaccine development

Studies of hepatitis C virus in chimpanzees and their importance for vaccine development
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DOI:
10.1159/000050040
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发表时间:
2001-03-01
期刊:
影响因子:
4.6
通讯作者:
Purcell, RH
Purcell, RH
中科院分区:
医学4区
文献类型:
--
作者:
Bukh, J;Forns, X;Purcell, RH

文献摘要

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丙型肝炎病毒(HCV)持续感染是世界范围内慢性肝病的一个重要原因。因此,开发预防丙肝病毒感染的疫苗,或至少防止丙肝病毒进展为慢性感染,是一个主要目标。潜在的HCV候选疫苗包括重组蛋白、重组病毒、DNA构建体、合成肽和病毒样颗粒。各种候选疫苗已被证明在动物(主要是小鼠)中产生体液和细胞免疫反应。然而,大多数候选疫苗在预防丙型肝炎病毒方面的效力尚未得到测试,因为黑猩猩是除人类之外唯一易感染丙型肝炎病毒的动物,不易获得,需要特殊设施,而且非常昂贵。黑猩猩感染过程的多样性与人类相似,该模型的详细研究开始确定可以终止HCV感染的免疫反应。与疫苗评估相关的是在不同HCV变异的黑猩猩中进行滴定,以提供具有良好特征的攻击池。此外,从感染了克隆病毒的黑猩猩身上产生的单克隆病毒库,现在可以在没有攻击病毒(准种)抗原多样性的混杂因素的情况下检查对丙型肝炎病毒的免疫力。迄今为止,在黑猩猩身上进行的疫苗试验都测试了使用各种形式的丙型肝炎病毒包膜蛋白进行免疫的有效性。版权所有(C) 2001 S. Karger AG,巴塞尔
Persistent infection with hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. Therefore, the development of vaccines to prevent HCV infection, or at least to prevent progression to chronicity, is a major goal. Potential HCV vaccine candidates include recombinant proteins, recombinant viruses, DNA constructs, synthetic peptides and virus-like particles. Various vaccine candidates have been shown to generate humoral and cellular immune responses in animals, primarily in mice. However, the efficacy of most vaccine candidates in protecting against HCV has not been tested because the chimpanzee, the only animal other than humans that is susceptible to HCV, is not readily available, requires special facilities, and is very expensive. The course of infection in chimpanzees is similar in its diversity to that in humans and detailed studies in this model are beginning to define the immune responses that can terminate HCV infection. Of relevance for vaccine evaluation was the titration in chimpanzees of different HCV variants to provide well-characterized challenge pools. In addition, monoclonal virus pools generated from chimpanzees infected with cloned viruses make it possible now to examine immunity to HCV without the confounding factor of antigenic diversity of the challenge virus (quasispecies). The vaccine trials performed in chimpanzees to date all have tested the efficacy of immunizations with various forms of the envelope proteins of HCV. Copyright (C) 2001 S. Karger AG, Basel.