Borrelial Factor H Binding Proteins

描述(申请人提供)：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。莱姆病现在是北美最常见的节肢动物传播疾病。已知有三种疏螺旋体可引起人类莱姆病：伯氏疏螺旋体、加里尼疏螺旋体和弗氏疏螺旋体。感染这些细菌是慢性的，可以持续几年。目前还没有商业上可用的莱姆病疫苗。因此，现有的莱姆病预防战略存在重大和严重的空白。我们最近鉴定了两种蛋白质，它们为疫苗开发提供了巨大的希望。这些蛋白，FHBP25和FHBP27(FHBP25/27)，通过与补体调节蛋白因子H结合促进免疫逃避，在莱姆病的发病机制中发挥关键作用。这降低了交替补体级联的效率，进而促进了慢性感染的建立。我们的假设是，基于FBHP25/27的疫苗在几个方面将优于其他潜在的疫苗。第一次接种FHBP25/27将产生杀菌抗体。其次，接种疫苗会导致产生抗体，从而阻断FHBP25/27结合H因子的能力，从而使螺旋体高度容易被调理和吞噬。最后，这种疫苗有可能在扁虱和哺乳动物环境中介导螺旋体的死亡。这项应用的目标是确定FHBP25/27疫苗的效力，并确定其保护相关因素。

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.