Where to Next? Research Directions after the First Hepatitis C Vaccine Efficacy Trial.

Where to Next? Research Directions after the First Hepatitis C Vaccine Efficacy Trial.
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DOI:
10.3390/v13071351
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发表时间:
2021-07-13
期刊:
Viruses
影响因子:
--
通讯作者:
Honegger JR
Honegger JR
中科院分区:
其他
文献类型:
--
作者:
Phelps CC;Walker CM;Honegger JR

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丙型肝炎病毒(HCV)被发现30年后,它仍然是世界范围内肝脏疾病的主要原因。鉴于许多国家尽管有有效的抗病毒疗法,但传播率仍然很高,因此有效的疫苗被视为消除HCV的关键。最近第一次预防慢性丙型肝炎病毒的疫苗有效性试验的失败证实了这种病毒将成为一个具有挑战性的疫苗靶点的怀疑。在这里,我们检查了已发表的数据,从这个第一个疗效试验沿着与早期的临床和临床前研究的候选疫苗,然后讨论三个关键的研究方向,预计将是重要的,在正在进行的和未来的HCV疫苗的发展。这些措施包括:1.设计对遗传多样性HCV基因型和亚型产生免疫应答的新型免疫原,2.除了细胞毒性和辅助性T细胞应答之外,引发针对包膜糖蛋白的广泛中和抗体的策略,以及3.在疫苗平台开发和早期免疫原性试验中,考虑最有HCV感染风险的个体(包括注射药物者)的独特免疫状态。
Thirty years after its discovery, the hepatitis C virus (HCV) remains a leading cause of liver disease worldwide. Given that many countries continue to experience high rates of transmission despite the availability of potent antiviral therapies, an effective vaccine is seen as critical for the elimination of HCV. The recent failure of the first vaccine efficacy trial for the prevention of chronic HCV confirmed suspicions that this virus will be a challenging vaccine target. Here, we examine the published data from this first efficacy trial along with the earlier clinical and pre-clinical studies of the vaccine candidate and then discuss three key research directions expected to be important in ongoing and future HCV vaccine development. These include the following: 1. design of novel immunogens that generate immune responses to genetically diverse HCV genotypes and subtypes, 2. strategies to elicit broadly neutralizing antibodies against envelope glycoproteins in addition to cytotoxic and helper T cell responses, and 3. consideration of the unique immunological status of individuals most at risk for HCV infection, including those who inject drugs, in vaccine platform development and early immunogenicity trials.
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