A RECOMBINANT HEPETITIS C VACCINE

重组丙型肝炎疫苗

• 批准号: 6055125
• 负责人: Darrell L Peterson
• 金额: $ 10万
• 依托单位: BIOCACHE PHARMACEUTICALS, LLC
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6055125
• 关键词: antibody titering; antiviral antibody; hepatitis C; hepatitis C virus; human tissue; laboratory mouse; protein sequence; recombinant virus; vaccine development; vector vaccine; virus antigen

The goal of this project is the development of a vaccine for the prevention of hepatitis C viral infection. The hepatitis C virus (HCV) is the primary etiologic agent of parenterally transmitted non-A, non-B hepatitis and is a major cause of hepatitis, cirrhosis, and hepatocellular carcinoma worldwide. HCV is highly variable due to mutations within the HCV envelope proteins. These mutations lead to viral "quasi-species" that are not neutralized by the antibodies formed in response to other quasi-species. The mutations occur predominantly within the hypervariable region 1 (HVR1), found at the amino terminus of the viral envelope protein, E2. Therefore, in order for any vaccine to be effective, it must elicit antibodies capable of neutralizing any of these quasi species, and thereby prevent establishment of the initial infection. The specific aims of this phase I project are to (1) construct a multideterminant antigen, consisting of a library of known as well as potential sequences of the HVR1; (2) present this library on a highly immunogenic on carrier moiety (Advanced Antigen Presentation Platform); (3) demonstrate that this construct binds anti-HCV antibodies; and (4) demonstrate that this immunogen induces high titre anti-HCV envelope antibodies. Phase II studies would involve assessing the protective efficacy of such an immunogen in susceptible hosts. PROPOSED COMMERCIAL APPLICATIONS: Over 300 million people are infected with HCV. Elimination of this disease will require a vaccine. Based on the hepatitis B virus this would represent about a $500 million dollar per year product.

该项目的目标是开发预防丙型肝炎病毒感染的疫苗。丙型肝炎病毒（HCV）是肠道外传播的非甲非乙型肝炎的主要病原体，并且是全世界肝炎、肝硬化和肝细胞癌的主要原因。由于HCV包膜蛋白内的突变，HCV是高度可变的。这些突变导致病毒“准种”，其不被响应于其他准种而形成的抗体中和。突变主要发生在高变区1（HVR 1）内，发现于病毒包膜蛋白E2的氨基末端。因此，为了使任何疫苗有效，它必须引发能够中和任何这些准种的抗体，从而防止初始感染的建立。该I期项目的具体目标是（1）构建多决定簇抗原，其由HVR 1的已知序列和潜在序列的文库组成;（2）将该文库呈递在高免疫原性的载体部分上，（Advanced Antigen Presentation Platform）;（3）证明该构建体结合抗HCV抗体;和（4）证明该免疫原诱导高滴度抗HCV包膜抗体。II期研究将涉及评估这种免疫原在易感宿主中的保护效力。建议的商业应用：超过3亿人感染HCV。消灭这种疾病需要疫苗。基于B型肝炎病毒，这将代表每年约5亿美元的产品。