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

该合同支持鉴定源自布氏疏螺旋体的人B细胞表位，以及了解抗体介导的保护性免疫的基础研究，以及抗体反应的病理后果。里程碑包括：1)表位鉴定；2)表位验证必须包括使用人类样本的体外评估；3)提交表位数据、计算机软件和结构数据到免疫表位数据库和分析资源；4)研究与新发现的表位相关的抗体引发的保护或发病机制。该合同将生成莱姆病病原体伯氏疏螺旋体OspA、OspC和DbpA三种抗原的全面人类B细胞表位图。该承包商将制作来自莱姆病患者的OspA、OpsC和DbpA人类单克隆抗体（HuMAbs）文库，并对与保护性免疫相关的HuMAbs功能活动进行表征。抗体对人类宿主抗原的交叉反应也将被研究，因为先前的研究揭示了抗体对病原体某些成分的反应与与莱姆病相关的衰弱的自身免疫样疾病症状之间的潜在关联。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.