Tickborne Disease: B cell epitope discovery and mechanisms of antibody Protection

母公司奖的目标是表位发现和验证，确定抗体对新鉴定的表位的作用机制，并将表位存入该机构的免疫表位数据库（IEDB.org）。承包者正在对从诊断为莱姆病的病人身上收集的大量血清样本进行筛查，这些病人是由病原体伯氏疏螺旋体引起的，以确定与预防莱姆病有关的抗体，以及可能引起莱姆病衰弱、慢性症状的抗体。在执行合同工作的过程中，他确定了两种蛋白质，这些蛋白质诱导了莱姆病关节炎和莱姆病神经疏螺旋体病患者血清中的抗体。这些发现与我们对慢性莱姆病症状病理学的理解密切相关，并可能为疫苗开发提供信息。莱姆病亚单位疫苗的合理设计将需要包括防止疏螺旋体感染的表位，但也应该排除可能通过诱导致病性抗体应答引起不良副作用的区域。目前还没有批准用于人类的疫苗。蜱虫种群继续增加，人类蜱传疾病的发病率相应增加。解决这一日益严重的公共卫生问题的能力取决于了解人类对感染的反应的研究，并将这些数据用作识别保护性成分的线索，以供作为候选疫苗进行测试。

The goal of the parent award is epitope discovery and validation, determination of mechanisms of action of antibodies to newly identified epitopes, and deposition on epitopes into the Agency’s Immune Epitope Database (IEDB.org). The Contractor is screening a large collection of serum samples collected from patients diagnosed with Lyme disease, caused by the pathogen, Borrelia burgdorferi, to identify antibodies associated with protection from Lyme disease, as well as antibodies that may induce debilitating, chronic symptoms of Lyme disease. During the course of performing the contracted work, he identified two proteins that induce antibodies found in the sera of patients with symptoms of Lyme arthritis and Lyme neuroborreliosis. These findings have strong relevance to our understanding of the pathology of chronic Lyme disease symptoms and may inform vaccine development. Rational design of Lyme subunit vaccines will need to include epitopes that prevent Borrelia infection but should also exclude regions that may cause adverse side effects through induction of pathogenic antibody responses. There is currently no vaccine approved for humans. The tick population continues to rise with a corresponding increase in the incidences of tickborne disease in humans. The ability to address this growing public health concern depends on research on understanding human responses to infection and using the data as clues for identification of protective components for testing as vaccine candidates.