治疗性丙型肝炎疫苗研究的新进展

Recent advances in studies on therapeutic hepatitis C virus vaccine

丙型肝炎是由丙型肝炎病毒 (HCV)感染引起的一种重要的世界性传染病 ,约 70 %～ 85 %的感染者发展为慢性肝炎 ,并可发展成肝硬化和肝癌等终末期肝病。目前尚没有预防HCV感染的疫苗。HCV感染后在体内持续存在和被清除的机制仍不明确。最近的研究提示 ,强烈的多特异性细胞免疫 ,特别是CTL反应在病毒的清除中扮演了重要角色。开发治疗性疫苗用于治疗慢性HCV感染是完全可行的 ,一个有效的HCV疫苗可能需要同时诱导高滴度的、长期存在的高交叉反应中和性抗体以及包含辅助T细胞和CTL细胞在内的广泛的、强烈的和多特异性的细胞免疫反应。另外 ,HCV疫苗只要能够防止HCV感染慢性化或治疗HCV引起的慢性丙型肝炎就可满足需要 ,并不一定要具有诱导清除性免疫的能力。本文概述了当前世界HCV疫苗研究的进展 ,特别是治疗性HCV疫苗的研究现状 。

Hepatitis C virus (HCV) infection is an important public health problem all over the world.Generally,HCV infection can cause acute self limited infections in a few infected patients,but more frequently,can cause chronic liver cell injury in other 70%～85% infected persons which maybe develop into cirrhosis and hepatocellular carcinoma in a high proportion.The mechanisms responsible for persistence or viral clearance are still unknown. But recent studies suggest that a vigorous multispecific cellular immune responses, particular those mediated by CD8 + cytotoxicity T lymphocytes (CTLs), are thought to play a pivotal role in the control of infection.To develop a useful therapeutic HCV vaccine for treatment of chronic HCV infection seems feasible.Indeed, induction of high titer,long lasting, and cross reactive neutralizing antibodies and a broad,stronger,multispecific cellular immune response that includes both helper T cells and CTLs may be necessary for an effective HCV vaccine.The final vaccine product may require multiple components that target various aspects of protective immunity.Finally, sterilizing immunity may not be necessary if a vaccine can be developed to prevent or therapy chronic infection of HCV,which is the major cause of morbidity and mortality from this disease.In this article,the advances of studies on HCV vaccine, especially the research situation of therapeutic vaccine,were discussed in details. Problems existing in the present and research strategies used in the future were also analyzed. [