Core-002 - Non-Human Primate Core

Core-002 - 非人类灵长类核心

• 批准号: 10428299
• 负责人: Christopher Yeh Chen
• 金额: $ 44.26万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10428299
• 关键词: Affect; Animal Model; Animals; Antibodies; Antibody Response; Antigens; Awareness; Biomedical Research; Blood; Blood specimen; Callithrix; Chronic; Chronic Hepatitis C; Clinical; Collection; Complex; Computing Methodologies; Data; Diagnosis; Experimental Designs; Genetic; Goals; Hepatitis C Vaccine; Hepatitis C virus; Human; Immune; Immune response; Immunization; Individual; Institution; Laboratories; Liver Cirrhosis; Macaca mulatta; Malignant neoplasm of liver; Modeling; Papio; Parents; Persons; Preclinical Testing; Predictive Value; Primates; Procedures; Recording of previous events; Regimen; Research; Research Institute; Research Personnel; Research Project Grants; Resources; Safety; Sampling; Site; Structure; Testing; Texas; Tissue Sample; Tissues; Toxic effect; Training; Vaccinated; Vaccination; Vaccine Antigen; Vaccine Research; Vaccines; Viral Antigens; base; biobank; chronic infection; design; experimental study; immunogenicity; member; nanoparticle; nonhuman primate; novel; novel vaccines; prevent; programs; protocol development; rational design; vaccine candidate

Summary Chronic hepatitis C virus (HCV) infection affects an estimated 71 million people worldwide. Chronic HCV infection frequently leads to liver cirrhosis and predisposes infected individuals to liver cancer. Approximately, 400,000 die from HCV-related complications a year. While a cure for HCV has recently been developed, access to and affordability of this treatment is limited. Furthermore, less than 20% of chronically infected individuals are aware of their diagnosis. Therefore, to eliminate HCV, a vaccine is still urgently needed. Because of the genetic variability of the HCV, to date HCV vaccines that have been tested clinically have not been successful at preventing chronic infection. This study takes advantage of recent structural data of HCV antigen complexes, computational methods to optimize antigen structure presentation, multivalent presentation of those antigens on self-assembling nanoparticles, and preclinical testing in a nonhuman primate model that has demonstrated strong predictive value of human antibody responses. Core C: NHP, based at the Southwest National Primate Research Center, will evaluate the immunogenicity of rationally designed HCV vaccine antigens and nanoparticles using a non-human primate (NHP) model, rhesus macaques, and collect blood and tissue samples to enable in-depth analysis of the immune responses elicited by the vaccine antigens in this P01 research program.

概括 慢性丙型肝炎病毒 (HCV) 感染影响全球估计 7100 万人。慢性丙肝病毒 感染经常导致肝硬化，并使感染者易患肝癌。 每年大约有 40 万人死于 HCV 相关并发症。虽然最近已经找到了治愈 HCV 的方法 尽管尚未开发出来，但这种治疗方法的获取和负担能力仍然有限。此外，不到 20% 慢性感染者知道自己的诊断结果。因此，要消灭HCV，就需要疫苗 仍然迫切需要。由于丙型肝炎病毒的遗传变异性，迄今为止，丙型肝炎病毒疫苗已 临床测试尚未成功预防慢性感染。本研究利用 HCV抗原复合物的最新结构数据、优化抗原结构的计算方法 这些抗原在自组装纳米粒子上的呈递、多价呈递以及临床前 在非人类灵长类动物模型中进行的测试已证明人类抗体具有强大的预测价值 回应。核心 C：NHP 位于西南国家灵长类动物研究中心，将评估 使用非人类合理设计的 HCV 疫苗抗原和纳米颗粒的免疫原性 灵长类动物（NHP）模型、恒河猴，并采集血液和组织样本以进行深入研究 分析 P01 研究计划中疫苗抗原引起的免疫反应。