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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 超过20亿人，占世界人口的三分之一，感染了结核分枝杆菌。每年有300万人死亡结核病。公共卫生问题正在加剧，因为大量使用抗生素，尤其是在艾滋病患者中，导致结核分枝杆菌的抗生素菌株。现有的疫苗有严重的局限性。该项目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TB的免疫相关性得到充分定义时，热休克蛋白65（Hsp65）的制剂将将含有HSP65 DNA序列的质粒与微分球中的免疫刺激蛋白一起封装，并作为疫苗进行测试。理由是质粒将迅速退出微球，集成到宿主DNA中，并产生HSP65，这将用作免疫原。后来，Hsp65蛋白将缓慢释放长达60天，作为抗原免疫的抗原。基于先前的小鼠实验，预计该疫苗具有预防活性，并且能够刺激与已经感染结核分枝杆菌的人的正常人更有效的免疫反应，从而降低了疾病的严重程度。