Borrelial Factor H Binding Proteins

疏螺旋体 H 因子结合蛋白

• 批准号: 6873738
• 负责人: RICHARD T MARCONI
• 金额: $ 22.13万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6873738
• 关键词: Borrelia; alternative complement pathway; antibacterial antibody; bacteria infection mechanism; bacterial proteins; bacterial vaccines; binding proteins; binding sites; laboratory mouse; protein binding; vaccine development

DESCRIPTION (provided by applicant): Lyme disease is a zoonotic disease that is transmitted to humans through the bite of infected Ixodes ticks. Lyme disease now represents the most common arthropod borne disease in N. America. Three species of Borrelia are known to cause Lyme disease in humans; B. burgdorferi, B. garinii and B. afzelii. Infection with these bacteria is chronic and can persist for several years. At the present time there is no commercially available Lyme disease vaccine. As a result there is a significant and serious void in the available preventive strategies for Lyme disease. We have recently characterized two proteins that offer great promise for vaccine development. These proteins, FHBP25 and FHBP27 (FHBP25/27), play a pivotal role in Lyme disease pathogenesis by promoting immune evasion through the binding of the complement regulatory protein factor H. Factor H bound to the spirochetal cell surface interacts with factor I which can then cleave the critical complement component, C3b. This decreases the efficiency of the alternate complement cascade, which in turn facilitates the establishment of chronic infection. It is our hypothesis that an FBHP25/27 based vaccine would be superior to other potential vaccines in several regards. First vaccination with FHBP25/27 will result in the production of bactericidal Ab. Second, vaccination will elicit the production of antibodies that would block the ability of FHBP25/27 to bind factor H and thereby render the spirochetes highly susceptible to opsonization and phagocytosis. Lastly, this vaccine has the potential to mediate spirochetes killing in both the tick and mammalian environments. The goal of this application is to determine the efficacy of an FHBP25/27 vaccine and determine its correlates of protection.

描述（由申请方提供）：莱姆病是一种人畜共患疾病，通过受感染的硬蜱叮咬传播给人类。 莱姆病现在是N.美国参考已知三种疏螺旋体引起人类莱姆病; B. burgdorferi，B. garinii和B. afzelii。这些细菌的感染是慢性的，可以持续数年。目前还没有可商购的莱姆病疫苗。因此，现有的莱姆病预防策略存在重大而严重的空白。我们最近发现了两种蛋白质，它们为疫苗开发提供了巨大的希望。这些蛋白质FHBP 25和FHBP 27（FHBP 25/27）通过结合补体调节蛋白因子H促进免疫逃避而在莱姆病发病机制中起关键作用。与螺旋体细胞表面结合的H因子与I因子相互作用，然后I因子可以切割关键的补体成分C3 b。这降低了交替补体级联反应的效率，这反过来又促进了慢性感染的建立。我们假设基于FBHP 25/27的疫苗在几个方面上级其他潜在的疫苗。首次接种FHBP 25/27将导致产生杀菌性Ab。其次，疫苗接种将引发抗体的产生，该抗体将阻断FHBP 25/27结合因子H的能力，从而使螺旋体对调理作用和吞噬作用高度敏感。最后，这种疫苗有可能介导蜱和哺乳动物环境中的螺旋体杀灭。本申请的目标是确定FHBP 25/27疫苗的功效并确定其保护相关因素。