TB VACCINE DEVELOPMENT IN NONHUMAN PRIMATE MODEL

非人灵长类动物模型中的结核病疫苗开发

• 批准号: 8357662
• 负责人: JOHN L VANDEBERG
• 金额: $ 26.39万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357662
• 关键词: Acquired Immunodeficiency Syndrome; Antibiotics; Antigens; DNA; DNA Sequence; Development; Disease; Drug Formulations; Encapsulated; Funding; Grant; Heat shock proteins; Immune; Immune response; Macaca mulatta; Microspheres; Modeling; Mus; Mycobacterium tuberculosis; National Center for Research Resources; Patients; Plasmids; Population; Primates; Principal Investigator; Proteins; Public Health; Research; Research Infrastructure; Resources; Secondary Immunization; Severity of illness; Source; Testing; Tuberculosis; Tuberculosis Vaccines; United States National Institutes of Health; Vaccines; base; cost; nonhuman primate; prophylactic; research study; resistant strain; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. More than 2 billion people, one-third of the world's population, are infected with Mycobacterium tuberculosis. Three million people die each year of TB. The public health problem is intensifying as the heavy use of antibiotics, particularly in AIDS patients, is leading to antibiotic resistant strains of M. tuberculosis. Existing vaccines have serious limitations. This project is determining the immunological responses of rhesus monkeys to M. tuberculosis infection, and the pathological development of disease, in more detail than has been done previously. When the immune correlates of TB have been well defined, a formulation of heat shock protein 65 (hsp65) and a plasmid containing the hsp65 DNA sequence will be encapsulated together with an immunostimulatory protein in microspheres, and tested as a vaccine. The rationale is that the plasmid will quickly exit the microspheres, integrate into host DNA, and produce hsp65, which will serve as an immunogen. Later, the hsp65 protein will be slowly released for up to 60 days, serving as antigen for a booster immunization. Based on prior experiments with mice, the vaccine is expected to have prophylactic activity and also to be capable of stimulating a more effective immune response than is normal in people who already are infected with M. tuberculosis, thereby reducing the severity of disease.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 超过 20 亿人，即世界人口的三分之一，感染了结核分枝杆菌。每年有三百万人死于结核病。由于抗生素的大量使用，特别是在艾滋病患者中，导致结核分枝杆菌产生抗生素耐药性，公共卫生问题正在加剧。现有的疫苗有严重的局限性。该项目正在比以前更详细地确定恒河猴对结核分枝杆菌感染的免疫反应以及疾病的病理发展。当结核病的免疫相关性得到明确确定后，热休克蛋白 65 (hsp65) 和含有 hsp65 DNA 序列的质粒的制剂将与免疫刺激蛋白一起封装在微球中，并作为疫苗进行测试。其基本原理是质粒会快速离开微球，整合到宿主 DNA 中，并产生 hsp65，作为免疫原。随后，hsp65蛋白将缓慢释放长达60天，作为加强免疫的抗原。根据之前对小鼠进行的实验，该疫苗预计具有预防活性，并且能够比已感染结核分枝杆菌的人激发更有效的免疫反应，从而降低疾病的严重程度。