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: 10655523
• 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/10655523
• 关键词: Acceleration; 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; Titrations; Vaccination; Vaccine Research; Vaccines; Validation; Variant; Viral Antigens; Virus; adaptive immune response; env Gene Products; human subject; improved; neutralizing antibody; neutralizing monoclonal antibodies; novel; pandemic virus; 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.

项目摘要 鉴于丙型肝炎病毒(丙型肝炎病毒)的持续流行，研发丙型肝炎疫苗是当务之急。 尽管病毒的遗传多样性非同寻常，但一些抗体具有广泛的中和作用，这意味着 这些抗体能够阻止基因多样化的丙型肝炎病毒分离株的感染。宽泛的刺激 中和抗体很可能是保护性丙型肝炎疫苗的主要成分，因此准确和 抗体滴度和中和广度的标准化测量是加速丙型肝炎疫苗的关键 发展。然而，目前还没有使用丙型肝炎病毒包膜蛋白或病毒的标准化验或试剂盒。 测定抗体效价或中和力。 我们建议建立一种用于定量检测丙型肝炎病毒的纯抗原和标准化免疫分析方法。 抗丙型肝炎病毒抗体对疫苗的反应，并开发标准化的丙型肝炎病毒中和小组 基因和表型不同的病毒用于定量中和抗体应答 接种疫苗。这些参照板可作为测量抗体效价的标准，并 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， 而丙型肝炎疫苗的开发也更加快速推进。 开发丙型肝炎病毒疫苗是当务之急。准确、标准化的测量 使用不同的丙型肝炎病毒分离株的抗体效价、中和效力和广度是评估丙型肝炎病毒的关键 候选疫苗和比较在不同实验室获得的结果。通过产生纯的丙型肝炎病毒抗原， 标准化的免疫分析和标准化的中和面板，我们将促进准确、可重复性 测量抗体反应，并加快丙型肝炎病毒疫苗的开发。