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: 10172194
• 负责人: Justin Richard Bailey
• 金额: $ 56.8万
• 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/10172194
• 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.

项目摘要 鉴于持续的丙型肝炎病毒（HCV）大流行，HCV疫苗的发展是紧迫的。 尽管该病毒具有非凡的遗传多样性，但某些抗体仍在广泛中和，这意味着 这些抗体能够通过遗传多样的HCV分离株阻断感染。广泛刺激 中和抗体可能是保护性HCV疫苗的主要组成部分，因此 抗体滴度的标准化测量和中和宽度是加速HCV疫苗的关键 发展。但是，目前尚无HCV信封蛋白或使用的病毒的标准测定法或面板 测量抗体滴度或中和。 我们在这里建议开发纯HCV抗原和标准化的免疫测定法，以定量 抗HCV抗体对疫苗接种的反应，并开发标准化的HCV中和面板 遗传和表型多样的病毒，用于量化中和抗体反应 疫苗接种。这些参考面板可以用作测量抗体滴度和 中和广度，这将允许在不同实验室获得的结果有意义的比较， 以及HCV疫苗开发的更快进步。 HCV疫苗的开发是紧迫的重点。准确和标准化的测量 滴度，使用多种HCV分离株对抗体的效力和广度是评估HCV的关键 候选疫苗和在不同实验室中获得的结果。通过纯HCV抗原的产生， 标准化的免疫测定和标准化的中和面板，我们将促进准确的，可重复的 抗体反应的测量，并加速HCV疫苗的开发。