Pierce Brian G, Keck Zhen-Yong, Foung Steven Kh
University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA.
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Curr Opin Virol. 2016 Oct;20:55-63. doi: 10.1016/j.coviro.2016.09.004. Epub 2016 Sep 19.
Hepatitis C virus (HCV) is a major global disease burden, often leading to chronic liver diseases, cirrhosis, cancer, and death in those infected. Despite the recent approval of antiviral therapeutics, a preventative vaccine is recognized as the most effective means to control HCV globally, particularly in at-risk and developing country populations. Here we describe the efforts and challenges related to the development of an HCV vaccine, which after decades of research have not been successful. Viral sequence variability poses a major challenge, yet recent research has provided unprecedented views of the atomic structure of HCV epitopes and immune recognition by antibodies and T cell receptors. This, coupled with insights from deep sequencing, robust neutralization assays, and other technological advances, is spurring research toward rationally HCV designed vaccines that preferentially elicit responses toward conserved epitopes of interest that are associated with viral neutralization and clearance.
丙型肝炎病毒（HCV）是一项重大的全球疾病负担，常常导致受感染者出现慢性肝病、肝硬化、癌症及死亡。尽管近期已批准了抗病毒疗法，但预防性疫苗仍被视为在全球控制HCV的最有效手段，尤其是在高危人群和发展中国家人群中。在此，我们描述了与HCV疫苗研发相关的努力和挑战，经过数十年研究，该疫苗尚未成功。病毒序列变异性构成了一项重大挑战，但近期研究已提供了HCV表位原子结构以及抗体和T细胞受体介导的免疫识别的前所未有的观点。这一点，再加上来自深度测序、强大的中和试验及其他技术进步的见解，正在推动针对合理设计的HCV疫苗的研究，这些疫苗优先引发针对与病毒中和及清除相关的感兴趣保守表位的反应。
