尽管丙型肝炎病毒(HCV)感染的治疗取得了显著进展,它仍然是一个巨大的全球健康负担,需要开发有效的预防性疫苗。这篇综述论文介绍了HCV疫苗候选和方法的现状,包括更传统的,基于灭活的病毒,更现代,如亚单位蛋白质,矢量化,基于核酸(DNA和mRNA)和病毒样颗粒。HCV疫苗的概念首先放在病毒遗传多样性和对HCV感染的适应性反应的背景下,了解这一点对于指导开发针对这种复杂病毒的有效疫苗至关重要。因为伦理层面在疫苗研究中也很重要,发展,和潜在的部署,我们也在本文中讨论这些问题。由于HCV的遗传变异及其逃避免疫反应的能力,预防HCV感染的安全有效疫苗的道路仍然坎坷。细胞培养系统的进展允许生产灭活的HCV疫苗候选物,可以在体外诱导交叉中和抗体,但是这是否可以预防人类感染尚不清楚。进入临床试验的亚单位蛋白候选疫苗引起HCV特异性体液和细胞反应,尽管它们是否转化为有效预防HCV感染或将感染进展为慢性状态仍有待证明。这种反应也是由经过临床试验的基于载体的候选疫苗诱导的。降低了病毒HCV载量,但不能预防慢性HCV感染。从临床前动物研究中不容易预测这些失望。使用病毒样颗粒的疫苗平台,DNA,mRNA为HCV疫苗提供了机会,但是他们在这方面的潜力还没有显示出来。确保设计的疫苗基于保守表位并引发广泛的中和免疫应答也是必需的。鉴于开发预防性HCV疫苗的失败,继续支持国家战略至关重要,包括筛查和治疗计划的资金。然而,这些行动可能不足以永久控制HCV负担,鼓励进一步动员大量资源用于HCV疫苗研究,作为消除病毒性肝炎作为全球公共卫生的缺失因素。
Despite remarkable progress in the treatment of hepatitis C virus (HCV) infection, it remains a significant global health burden, necessitating the development of an effective prophylactic vaccine. This review paper presents the current landscape of HCV vaccine candidates and approaches, including more traditional, based on inactivated virus, and more modern, such as subunit protein, vectored, based on nucleic acids (DNA and mRNA) and virus-like particles. The concept of the HCV vaccine is first put in the context of viral genetic diversity and adaptive responses to HCV infection, an understanding of which is crucial in guiding the development of an effective vaccine against such a complex virus. Because ethical dimensions are also significant in vaccine research, development, and potential deployment, we also address them in this paper. The road to a safe and effective vaccine to prevent HCV infection remains bumpy due to the genetic variation of HCV and its ability to evade immune responses. The progress in cell-culture systems allowed for the production of an inactivated HCV vaccine candidate, which can induce cross-neutralizing antibodies in vitro, but whether this could prevent infection in humans is unknown. Subunit protein vaccine candidates that entered clinical trials elicited HCV-specific humoral and cellular responses, though it remains to be shown whether they translate into effective prevention of HCV infection or progression of infection to a chronic state. Such responses were also induced by a clinically tested vector-based vaccine candidate, which decreased the viral HCV load but did not prevent chronic HCV infection. These disappointments were not readily predicted from preclinical animal studies. The vaccine platforms employing virus-like particles, DNA, and mRNA provide opportunities for the HCV vaccine, but their potential in this context has yet to be shown. Ensuring the designed vaccine is based on conserved epitope(s) and elicits broadly neutralizing immune responses is also essential. Given failures in developing a prophylactic HCV vaccine, it is crucial to continue supporting national strategies, including funding for screening and treatment programs. However, these actions are likely insufficient to permanently control the HCV burden, encouraging further mobilization of significant resources for HCV vaccine research as a missing element in the elimination of viral hepatitis as a global public health.