Core-002 - Non-Human Primate Core

Core-002 - 非人类灵长类核心

• 批准号: 10557875
• 负责人: Christopher Yeh Chen
• 金额: $ 42.33万
• 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/10557875
• 关键词: Affect; Animal Euthanasia; Animal Model; Animals; Antibodies; Antibody Response; Antigens; Awareness; Biomedical Research; Blood; Blood specimen; Breeding; Callithrix; Chronic; Chronic Hepatitis C; Clinical; Collaborations; 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; biobank; chronic infection; design; experimental study; immunogenicity; member; nanoparticle; nonhuman primate; novel; novel vaccines; prevent; programs; protocol development; rational design; self assembly; 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）感染影响了全球约有7100万人。慢性HCV 感染经常导致肝硬化，并使感染的个体容易受到肝癌的感染。 大约每年与HCV相关并发症死亡40万。虽然最近可以治愈HCV 已开发，获得此治疗的可承受能力是有限的。此外，不到20％ 长期感染的人知道他们的诊断。因此，为了消除HCV，疫苗是 仍然迫切需要。由于HCV的遗传变异性，迄今为止的HCV疫苗已经 在临床上测试尚未成功预防慢性感染。这项研究利用了 HCV抗原复合物的最新结构数据，优化抗原结构的计算方法 呈现，这些抗原在自组装纳米颗粒上的多价表示以及临床前 在非人类灵长类动物模型中测试，该模型表现出强烈的人类抗体预测价值 回答。 Core C：总部位于西南国家灵长类动物研究中心的NHP将评估 使用非人类的理性设计的HCV疫苗抗原和纳米颗粒的免疫原性 灵长类动物（NHP）模型，恒河猕猴和收集血液和组织样品以实现深入 疫苗抗原在该P01研究计划中引起的免疫反应的分析。