Outer membrane lipoproteins of Borrelia burgdorferi

描述（由申请人提供）：莱姆病由节肢动物传播的伯氏疏螺旋体螺旋体引起，是一种多系统疾病，可导致皮肤、心脏、神经和风湿病表现。由于美国每年报告的莱姆病病例超过15，000例，因此预防莱姆病的安全有效疫苗已成为公共卫生优先事项。在这方面，许多研究表明，这种生物体的外膜脂蛋白可用作有效的疫苗试剂。事实上，外表面脂蛋白A（OspA）已被证明可以保护动物和人类免受B的感染。burgdorferi，并在几年前被批准用于人类。然而，最近的事件导致OspA疫苗被撤出市场，现在不再向公众提供。因此，B中的一个主要重点。burgdorferi的研究一直在开发一种新的疫苗，可以作为一种安全有效的第二代预防莱姆病。从B开始。虽然伯氏疏螺旋体是细胞外病原体，并且体液免疫已显示出针对该生物体的保护性，但疫苗研究围绕鉴定疏螺旋体抗原，所述疏螺旋体抗原是（i）表面暴露的，（ii）在疏螺旋体螺旋体的不同菌株和基因种之间保守的，以及（iii）在蜱传播和哺乳动物感染期间表达的。我们最近使用微阵列实验来帮助识别新的候选疫苗分子，我们已经在初步研究中显示了这些分子的表面暴露，命名为BbA36，BbA69和BbI42。支持这些抗原可能是第二代莱姆病疫苗原的事实是，针对所有三种抗原产生的抗体可以杀死B。burgdorferi在体外培养期间。因此，该集中应用的主要目标是通过（i）确定它们在B的整个地方病生命周期中的细胞位置来进一步表征这些表面暴露的蛋白质。burgdorferi，（ii）研究了不同菌株和基因种间B. burgdorferi，和（iii）评估它们保护小鼠和非人灵长类动物免受实验性莱姆病的能力。拟议的研究应该会产生候选疫苗分子，可以在人体中进一步测试其安全性和有效性，以用作第二代莱姆病疫苗。

DESCRIPTION (provided by applicant): Lyme disease, caused by the arthropod-borne spirochete Borrelia burgdorferi, is a multisystem disorder that can lead to dermatologic, cardiac, neurologic, and rheumatologic manifestations. With more than 15,000 cases reported in the United States every year, a safe and effective vaccine for preventing Lyme disease has become a public health priority. In this regard, numerous lines of investigation indicate that outer membrane lipoproteins of this organism can be used as effective vaccine reagents. In fact, outer surface lipoprotein A (OspA) has been shown to protect animals and humans from infection with B. burgdorferi, and was approved for use in humans several years ago. However, recent events have led to the OspA vaccine being taken off the market and it is now no longer available to the general public. Therefore, a major emphasis in B. burgdorferi research has been to develop a new vaccine that could be used as a safe and effective second-generation preventative against Lyme disease. Since B. burgdorferi is an extracellular pathogen, and humoral immunity has been shown to be protective against this organism, vaccine studies have revolved around identifying a borrelial antigen that is (i) surface-exposed, (ii) conserved among different strains and genospecies of Borrelia spirochetes, and (iii) expressed during tick transmission and mammalian infection. We recently used microarray experiments to help identify new candidate vaccine molecules that we have shown to be surface-exposed in preliminary studies, designated BbA36, BbA69, and BbI42. Supporting the fact that these antigens may be possible 2nd generation Lyme disease vaccinogens is the fact that antibodies generated against all three can kill B. burgdorferi during in vitro cultivation. Therefore, the major goal of this focused application is to further characterize these surface-exposed proteins by (i) determining their cellular location throughout the enzootic life-cycle of B. burgdorferi, (ii) examining their overall genetic conservation among different strains and genospecies of B. burgdorferi, and (iii) assessing their ability to protect mice and non-human primates from experimental Lyme disease. The proposed studies should lead to candidate vaccine molecules that can be further tested for safety and efficacy in humans for use as a second- generation Lyme disease vaccine.