University of Oxford, NDM and Jenner Institute, Peter Medawar Building, South Parks Road, Oxford, OX1 3SY, UK.
Expert Opin Biol Ther. 2013 Aug;13(8):1109-24. doi: 10.1517/14712598.2013.791277. Epub 2013 May 7.
With 3 - 4 million new infections occurring annually, hepatitis C virus (HCV) is a major global health problem. There is increasing evidence to suggest that HCV will be highly amenable to a vaccine approach, and despite advances in treatment, a vaccine remains the most cost-effective and realistic means to significantly reduce the worldwide mortality and morbidity associated with persistent HCV infection.
In this review we discuss immune responses to HCV during natural infection, and describe how they may inform vaccine design. We introduce the current candidate vaccines for HCV and compare how these fare against the expected requirements of an effective prophylactic HCV vaccine in relation to the breadth, functionality, magnitude and phenotype of the vaccine-induced immune response.
Although the correlates of immune protection against HCV are not completely defined, we now have vaccine technologies capable of inducing HCV-specific adaptive immune responses to an order of magnitude that are associated with protection during natural infection. The challenge next is to i) establish well-characterised cohorts of people at risk of HCV infection for vaccine efficacy testing and ii) to better understand the correlates of protection in natural history studies. If these can be achieved, a vaccine against HCV appears a realistic goal.
每年有 300 万至 400 万例新感染病例，丙型肝炎病毒 (HCV) 是一个全球性的主要健康问题。越来越多的证据表明，丙型肝炎病毒将非常适合疫苗接种方法，尽管治疗取得了进展，但疫苗仍然是降低与持续 HCV 感染相关的全球死亡率和发病率的最具成本效益和最现实的手段。
在这篇综述中，我们讨论了 HCV 感染期间的免疫反应，并描述了它们如何为疫苗设计提供信息。我们介绍了当前 HCV 的候选疫苗，并比较了这些疫苗在与预防 HCV 感染相关的预期要求方面的表现，包括疫苗诱导免疫反应的广度、功能、幅度和表型。
尽管针对 HCV 的免疫保护相关因素尚未完全确定，但我们现在拥有能够诱导 HCV 特异性适应性免疫反应的疫苗技术，其数量级与自然感染期间的保护相关。下一步的挑战是：i）建立具有明确特征的 HCV 感染风险人群队列，以进行疫苗功效测试；ii）更好地理解自然史研究中的保护相关因素。如果这些能够实现，针对 HCV 的疫苗似乎是一个现实的目标。
