A virus-like particle vaccine for hepatitis C virus.

目的是评价丙型肝炎病毒(HCV)病毒样颗粒(VLP)疫苗的有效性。在澳大利亚，每年约有10,000人感染丙型肝炎病毒，其中约8,000人将发展为持续性感染。因此，目前澳大利亚有15万至20万丙型肝炎病毒携带者，全球有5亿人。这些人代表了感染源。虽然主要的传播途径是血液和血液制品，但在血库中进行丙型肝炎病毒筛查的出现降低了从这一来源感染的风险。然而，许多静脉注射吸毒者共用针头，尽管这种情况并不常见，但将病毒传染给携带者的配偶是很常见的。此外，大约20%的丙型肝炎病毒携带者没有公认的危险因素，这些人是如何感染的还不清楚。该病毒向住院患者和门诊患者的传播也得到了很好的认识，因此，显然迫切需要一种疫苗。然而，由于丙型肝炎病毒不能在实验室中培养，因此不可能开发出传统的疫苗；此外，由于一部分从丙型肝炎病毒感染中恢复的患者没有特定的免疫力，因此可能会再次感染，因此疫苗的设计带来了许多问题。因此，与旨在产生细胞免疫反应的疫苗相比，基于中和抗体开发的疫苗不太可能有效。VLP诱导有效的细胞免疫反应，我们计划使VLP由牛乳头瘤病毒(BPV)的L1蛋白组成，该蛋白与高度免疫原性的丙型肝炎病毒核心蛋白或一系列蛋白片段(多表位)融合。将这些VLP接种实验室小鼠，并测量其细胞免疫反应。然后，疫苗将被接种给丙型肝炎病毒携带者，以确保产品的安全性和免疫效力。这将进行血清学和临床评估。

The aim is to evaluate the efficiency of a virus-like particle (VLP) vaccine for hepatitis C virus (HCV). HCV infects about 10,000 people every year in Australia and approximately 8, 000 of these will develop persistent infection. As a result, there are currently 150,000-200,000 HCV carriers in Australia and 500 million worldwide. These individuals represent a source of infection. Although the major route for transmission is blood and blood products, the advent of HCV screening in the blood banks has reduced the risk of infection from this source. However, many intravenous drug users (IVD) share needles and although it is not common, transmission to spouses of carriers is well recognised. In addition, approximately 20% of HCV carriers have no recognised risk factor and it is unclear how these individuals became infected. Transmission of the virus to hospital inpatients and outpatients is also well recognised and as a result, it is clear that a vaccine is urgently required. However, as HCV cannot be cultured in the laboratory, it is impossible to develop a traditional vaccine; furthermore, because a proportion of patients who recover from HCV infection have no specific immunity and thus can be re-infected, the design of a vaccine presents a number of problems. Thus a vaccine which is based on the development of neutralising antibody is unlikely to be effective, in contrast to a vaccine which is designed to generate a cellular immune response. VLPs induce an effective cellular immune response and we plan to make VLPs composed of the L1 protein of bovine papillomavirus (BPV) which is fused to the highly immunogenic HCV core protein or to a string of protein segments (polytope). Laboratory mice will be vaccinated with these VLP and the cellular immune response measured. The vaccine will then be administered to HCV carriers to ensure the safety and the immunological efficacy of the product. This will be assessed serologically and clinically.