Lyme Disease: B cell epitope discovery and mechanisms of antibody protection

该合同支持识别来自伯氏疏螺旋体的人类B细胞表位，以及了解抗体介导的保护性免疫以及抗体反应的病理后果的基础研究。里程碑包括1)表位识别；2)表位验证，必须包括使用人类样本进行体外评估；3)向免疫表位数据库和分析资源提交表位数据、计算机软件和结构数据；以及4)帮助理解与新识别的表位相关的抗体所引发的保护或致病机制的研究。这项合同将制作来自莱姆病病原体伯氏疏螺旋体的三种抗原OspA、OspC和DbpA的全面人类B细胞表位图。承包商将生产来自莱姆病患者的OspA、OPSC和DbpA人类单抗(HuMAbs)库，并表征HuMAb与保护性免疫相关的功能活性。还将调查抗体对人类宿主抗原的交叉反应，因为先前的研究揭示了对病原体某些成分的抗体反应与与莱姆病相关的衰弱的自身免疫性疾病症状之间的潜在联系。拟议合同的结果将有助于莱姆病诊断、疫苗和免疫疗法的发展。

This contract supports the identification of human B cell epitopes derived from Borrelia bugdorferi, coupled with basic studies to understand protective immunity mediated by antibodies, as well as pathological consequences of antibody responses. Milestones include 1) epitope identification; 2) epitope validation that must include in vitro evaluation using human samples; 3) submission of epitope data, computer software, and structural data to the Immune Epitope Database and Analysis Resource; and 4) studies to help understand the mechanisms of protection or pathogenesis elicited by antibodies associated with the newly identified epitopes. This contract will produce comprehensive human B cell epitope maps of three antigens, OspA, OspC and DbpA, from Borrelia burgdorferi, the causative agent of Lyme disease. The contractor will produce libraries of OspA, OpsC and DbpA human monoclonal antibodies (HuMAbs) from Lyme disease patients and characterize the HuMAbs for functional activities associated with protective immunity. Antibody cross-reactivities to human host antigens will also be investigated, as prior studies reveal potential associations between antibody responses to some components of the pathogen and the debilitating, autoimmune-like disease symptoms associated with Lyme Disease. Results of the proposed contract will contribute to development of Lyme disease diagnostics, vaccines, and immunotherapies.