Development of standardized immunoassays and virus panels for HCV vaccine research

开发用于 HCV 疫苗研究的标准化免疫测定和病毒组

• 批准号: 10456321
• 负责人: Justin Richard Bailey
• 金额: $ 54.2万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-23 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456321
• 关键词: Adopted; Antibodies; Antibody Response; Antibody titer measurement; Antigens; Biological Assay; Cells; Data; Development; Generations; Genetic Polymorphism; Genetic Variation; Genotype; Glycoproteins; Hepatitis C Antibodies; Hepatitis C Vaccine; Hepatitis C virus; Immune; Immune Plasma; Immunoassay; Individual; Infection; Laboratories; Laboratory Research; Measurement; Measures; Phenotype; Play; Preparation; Reagent; Reproducibility; Role; Standardization; Vaccination; Vaccine Research; Vaccines; Validation; Variant; Viral Antigens; Virus; adaptive immune response; base; env Gene Products; human subject; improved; neutralizing antibody; neutralizing monoclonal antibodies; novel; pandemic disease; vaccine candidate; vaccine development; virus envelope

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.

项目概要 鉴于丙型肝炎病毒（HCV）的持续流行，HCV疫苗的开发是当务之急。 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作用，这意味着 这些抗体能够阻止遗传多样性 HCV 分离株的感染。广泛刺激 中和抗体可能是保护性 HCV 疫苗的主要成分，因此准确且可靠 抗体滴度和中和广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 HCV 包膜蛋白或病毒的标准测定或组合 测量抗体滴度或中和。 我们在此建议开发纯 HCV 抗原和标准化免疫测定法来定量 抗 HCV 抗体对疫苗接种的反应，并开发标准化的 HCV 中和组 遗传和表型多样化的病毒，用于量化中和抗体反应 疫苗接种。这些参考组可以用作抗体滴度测量的标准 中和广度，这将允许对不同实验室获得的结果进行有意义的比较， HCV 疫苗研发取得更快进展。 开发 HCV 疫苗是当务之急。准确、标准化的测量 使用不同 HCV 分离株的抗体滴度、中和效力和广度是评估 HCV 的关键 候选疫苗并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小组，我们将促进准确、可重复的 测量抗体反应，并加速 HCV 疫苗的开发。