THE 2.9 LIPOPROTEIN FAMILY OF BORRELIA BURGDORFERI

描述(改编自申请者摘要)：莱姆病，由 致病性伯氏疏螺旋体是一种重要的公共卫生疾病。 值得进一步努力的问题，朝着改善的发展 疫苗和新的诊断方法。调查人员发现了一个新的家族 脂蛋白(称为“2.9”脂蛋白)似乎是“不同的” 由Bb表达；即这些脂蛋白中的一些以Bb的形式表达 在体外复制(类似于BB生命周期的节肢动物阶段) 而另一些则在体内以BB复制的形式表达(即在 哺乳动物感染阶段)。令人信服的初步数据已经支持 预期这2.9个脂蛋白在体内表达可能会作为 有效的疫苗和血清诊断试剂。 这项建议的具体目的是：(1)确定和比较 Bb的2.9种脂蛋白的体外与体内表达模式 菌株297；(2)评估2.9脂蛋白(特别是那些 BB在体内条件下表达的)在BB中表面暴露，从而 保护性抗体的目标(即候选疫苗)； 2.9脂蛋白作为莱姆病血清学诊断新抗原的研究 疾病；以及(4)检查同源2.9脂蛋白的存在 (尤其是那些具有疫苗生成和诊断重要性的) 伯氏杆菌的Sensu Lato基因种。 这一提议的一个特别新颖的方面是它依赖于一种新的动物 可获得“哺乳动物宿主适应的”强毒BB的模型系统 从大鼠或兔的腹膜腔中提取的数量足以识别2.9 BB的脂蛋白在体内表达。利用这些新动物的力量 区分“体外”和“体内”表达的模型系统 2.9脂蛋白的模式在于抗原在 可以有选择地选择BB人畜共患病生命周期的每一个或两个阶段 解决莱姆病疫苗开发中的当代问题和 血清学诊断。

DESCRIPTION (Adapted from the Applicant's Abstract): Lyme disease, caused by the pathogenic spirochete Borrelia burgdorferi (Bb) is a major public health problem which warrants further efforts towards the development of improved vaccines and new diagnostics. The investigators have discovered a new family of lipoproteins (termed "2.9" lipoproteins) that appear to be "differentially expressed" by Bb; i.e., some of these lipoproteins are expressed as Bb replicates in vitro (analogous to the arthropod phase of Bb's life cycle) whereas others are expressed as Bb replicates "in vivo" (i.e., during the mammalian phase of infection). Compelling preliminary data already support the expectation that those 2.9 lipoproteins expressed "in vivo" may serve as effective vaccines and serodiagnostic reagents. The Specific Aims of this proposal are: (1) To determine and compare the "in vitro" versus "in vivo" expression patterns for the 2.9 lipoproteins of Bb strain 297; (2) To assess whether the 2.9 lipoproteins (particularly those express by Bb under "in vivo" conditions) are surface-exposed in Bb and thus targets for protective antibodies (i.e., vaccine candidates); (3) To investigate the 2.9 lipoproteins as new antigens for the serodiagnosis of Lyme disease; and (4) To examine the presence of homologous 2.9 lipoproteins (particularly those with vaccinogenic and diagnostic importance ) in all three sensu lato genospecies of B. burgdorferi. A particularly novel aspect of this proposal is its reliance upon a new animal model system in which virulent, "mammalian host-adapted" Bb can be obtained from rat or rabbit peritoneal chambers in quantities sufficient to identify 2.9 lipoproteins of Bb expressed "in vivo." The power of utilizing these new animal model systems for sorting out the "in vitro" versus "in vivo" expression patterns for 2.9 lipoproteins lies in the fact that antigens expressed during each or both phases of the zoonotic life cycle of Bb can be selectively chosen to address contemporary issues in Lyme disease vaccine development and serodiagnosis.