Development of standardized immunoassays and virus panels for HCV vaccine research

项目摘要 鉴于丙型肝炎病毒（HCV）的持续流行，HCV疫苗的开发是一个紧迫的优先事项。 尽管该病毒具有非凡的遗传多样性，但一些抗体具有广泛的中和性，这意味着 这些抗体能够阻断遗传多样性HCV分离株的感染。刺激广泛 中和抗体很可能是保护性HCV疫苗的主要成分，因此准确且 抗体滴度和中和宽度的标准化测量是加速HCV疫苗接种的关键 发展然而，目前还没有使用标准的HCV包膜蛋白或病毒检测试剂盒或试剂盒 以测量抗体滴度或中和。 我们建议开发纯HCV抗原和标准化的免疫测定方法，用于定量检测HCV抗原。 抗-HCV抗体对疫苗接种的应答，并开发一个标准化的HCV中和面板， 用于定量中和抗体应答的遗传和表型多样性病毒， 预防针这些参考板可用作测量抗体滴度的标准， 中和广度，这将使不同实验室获得的结果进行有意义的比较， HCV疫苗开发的快速进展。 开发HCV疫苗是当务之急。准确和标准化的测量 使用不同HCV分离株检测抗体的滴度、中和效力和广度是评价HCV的关键 候选疫苗和比较不同实验室获得的结果。通过产生纯HCV抗原， 标准化的免疫测定和标准化的中和板，我们将促进准确，可重复的 抗体反应的测量，并加速HCV疫苗的开发。

Project Summary Given the ongoing hepatitis C virus (HCV) pandemic, HCV vaccine development is an urgent priority. Despite the extraordinary genetic diversity of the virus, some antibodies are broadly neutralizing, meaning that these antibodies are able to block infection by genetically diverse HCV isolates. Stimulation of broadly neutralizing antibodies is likely to be a major component of a protective HCV vaccine, so accurate and standardized measurement of antibody titers and neutralization breadth is key to accelerating HCV vaccine development. However, there is currently no standard assay or panel of HCV envelope proteins or viruses used to measure antibody titers or neutralization. We propose here to develop pure HCV antigens and a standardized immunoassay for quantification of anti-HCV antibody responses to vaccination, and to develop a standardized HCV neutralization panel with genetically and phenotypically diverse viruses for quantification of neutralizing antibody responses to vaccination. These reference panels could be adopted as a standard for measurement of antibody titers and neutralizing breadth, which would allow meaningful comparisons of results obtained in different laboratories, and more rapid advancement of HCV vaccine development. Development of an HCV vaccine is an urgent priority. Accurate and standardized measurement of the titers, neutralizing potency and breadth of antibodies using diverse HCV isolates is key to evaluating HCV vaccine candidates and comparing results obtained in different laboratories. By generation of pure HCV antigens, a standardized immunoassay, and a standardized neutralization panel, we will facilitate accurate, reproducible measurements of antibody responses, and accelerate HCV vaccine development.