THE 2.9 LIPOPROTEIN FAMILY OF BORRELIA BURGDORFERI

2.9 伯氏疏螺旋体脂蛋白家族

• 批准号: 6534162
• 负责人: MICHAEL V. NORGARD
• 金额: $ 36.13万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6534162
• 关键词: Borrelia; Lyme disease; bacterial antigens; bacterial proteins; gene expression; laboratory rabbit; laboratory rat; nonblood lipoprotein; serology /serodiagnosis; vaccine development; virulence

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.

描述（改编自申请人的摘要）：莱姆病，由 致病性螺旋体伯氏疏螺旋体 (Bb) 是一个主要的公共卫生问题 需要进一步努力开发改进的问题 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“有差异” 由 Bb 表达”；即，其中一些脂蛋白表达为 Bb 体外复制（类似于 Bb 生命周期的节肢动物阶段） 而其他表达为 Bb 复制“体内”（即，在 哺乳动物感染阶段）。令人信服的初步数据已经支持了 期望那些“体内”表达的2.9脂蛋白可以作为 有效的疫苗和血清诊断试剂。 该提案的具体目标是： (1) 确定并比较“in Bb 2.9 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 在“体内”条件下由 Bb 表达）在 Bb 中表面暴露，因此 保护性抗体的目标（即候选疫苗）； (3) 至 研究 2.9 脂蛋白作为莱姆病血清学诊断的新抗原 疾病; (4) 检查同源 2.9 脂蛋白的存在 （特别是那些具有疫苗原性和诊断重要性的）在所有三个方面 伯氏疏螺旋体意义的基因种。 该提案的一个特别新颖的方面是它对一种新动物的依赖 模型系统，其中可以获得有毒的“哺乳动物宿主适应”Bb 来自大鼠或兔子腹膜室的数量足以识别 2.9 Bb 的脂蛋白“在体内”表达。利用这些新动物的力量 用于分类“体外”与“体内”表达的模型系统 2.9 脂蛋白的模式在于以下事实：抗原在 Bb人畜共患生命周期的每个或两个阶段都可以选择性地选择 解决莱姆病疫苗开发中的当代问题 血清诊断。