Borrelial Factor H Binding Proteins

疏螺旋体 H 因子结合蛋白

• 批准号: 6759626
• 负责人: RICHARD T MARCONI
• 金额: $ 18.38万
• 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 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6759626
• 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（由申请人提供）：莱姆病是一种人畜共患病，通过被感染的ixodes tick虫咬伤传播给人类。 莱姆病现在是美国北部最常见的节肢动物传播疾病。已知三种伯碱会引起人类莱姆病。 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，尚无市售莱姆病疫苗。结果，在莱姆病的可用预防策略中存在重大而严重的空隙。我们最近对两种蛋白质进行了表征，这些蛋白质为疫苗开发提供了巨大的希望。这些蛋白质，FHBP25和FHBP27（FHBP25/27），通过通过补体调节蛋白因子H.因子H.因子H.因子H.因子与螺旋裂细胞表面与因子I与因子I相互作用的结合而在莱姆病发病机理中起关键作用，然后与螺旋体表面相互作用，从而可以切断临界辅助组件，C3B c3b c3b c3 b。这降低了替代补体级联反应的效率，这反过来促进了慢性感染的建立。我们的假设是，在几种方面，基于FBHP25/27的疫苗将优于其他潜在疫苗。 FHBP25/27的首次疫苗接种将导致杀菌AB的产生。其次，疫苗接种将引起抗体的产生，该抗体将阻止FHBP25/27结合H的能力，从而使螺旋体高度容易受到调理和吞噬作用。最后，这种疫苗有可能介导tick和哺乳动物环境中的螺旋体杀死。该应用的目的是确定FHBP25/27疫苗的功效，并确定其保护的相关性。