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

莱姆病：B 细胞表位发现和抗体保护机制

基本信息

批准号：
10021076
负责人：
Nicholas J. Mantis
金额：
$ 166.08万
依托单位：
NYSDOH/HEALTH RESEARCH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-16 至 2020-09-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10021076
关键词：
Adherence Antibodies Antibody Response Antibody-mediated protection Antigens Archives Artificial Feeding Autoimmune Process B-Lymphocyte Epitopes B-Lymphocytes Biological Assay Blood Borrelia Borrelia burgdorferi Cell Line Complement Computer software Connecticut Contractor Contracts Coupled Data Databases Development Diagnostic Disease Epitopes European Evaluation Extracellular Matrix Heart Human Hydrogen Immune Immunity Immunotherapy In Situ In Vitro Infection Joints Libraries Lyme Disease Maps Mass Spectrum Analysis Massachusetts Mediating Mus Needles New York OspA protein OspC protein Pathogenesis Pathologic Patients Resolution Resources Sampling Serum Stream Structure Structure of parenchyma of lung Support Contracts Ticks Tissues Vaccines Validation Variant X-Ray Crystallography associated symptom base cross reactivity human monoclonal antibodies in vivo Model mouse model pathogen transmission process

项目摘要

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.

该合同支持鉴定源自伯氏虫的人类B细胞表位，再加上基础研究，以了解抗体介导的保护性免疫，以及抗体反应的病理后果。里程碑包括1）表位识别； 2）表位验证必须包括使用人类样品进行体外评估； 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； 4）研究有助于了解与新确定的表位相关的抗体引起的保护或发病机理的机理。该合同将产生来自莱姆病的致病药物Borrelia Burgdorferi的三个抗原，OSPA，OSPC和DBPA的全面人类B细胞表位图。承包商将从莱姆病患者中生产OSPA，OPSC和DBPA人类单克隆抗体（Humabs）的文库，并为与保护性免疫相关的功能活动表征Humabs。对人类宿主抗原的抗体交叉反应性也将进行研究，因为先前的研究揭示了对病原体某些成分的抗体反应与衰弱的，自身免疫性疾病症状与莱姆病有关的抗体。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。