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

• 批准号: 10912412
• 负责人: Nicholas J. Mantis
• 金额: $ 186.52万
• 依托单位: NYSDOH/HEALTH RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2024-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10912412
• 关键词: Adherence; Antibodies; Antibody Response; Antibody-mediated protection; Antigens; Archives; Artificial Feeding; Autoimmune; B-Lymphocyte Epitopes; B-Lymphocytes; Biological Assay; Blood; Borrelia; Borrelia afzelii; Borrelia burgdorferi; Borrelia garinii; Cell Line; Complement; Computer software; Connecticut; Contractor; Contracts; Coupled; Data; Databases; Development; Disease; Epitope Mapping; Epitopes; European; Evaluation; Extracellular Matrix; Heart; Human; Hydrogen; Immune; Immunity; Immunotherapy; In Situ; In Vitro; Infection; Joints; Libraries; Lyme Disease; Lyme disease diagnostic; Maps; Mass Spectrum Analysis; Massachusetts; Mediating; Mus; Needles; New York; OspA protein; OspC protein; Pathogenesis; Pathologic; Patients; Predisposition; Resolution; Resources; Sampling; Serum; Stream; Structure of parenchyma of lung; Support Contracts; Ticks; Tissues; Vaccines; Validation; Variant; X-Ray Crystallography; associated symptom; cross reactivity; human monoclonal antibodies; in vivo Model; mouse model; pathogen; transmission process

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.

该合同支持鉴定来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以及抗体应答的病理后果的基础研究。重要性包括1）表位鉴定; 2）表位验证，其必须包括使用人样品的体外评价; 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）研究以帮助理解与新鉴定的表位相关的抗体引起的保护或发病机制。该合同将产生全面的人类B细胞表位图的三个抗原，OspA，OspC和DbpA，从莱姆病的病原体伯氏疏螺旋体。承包商将生产来自莱姆病患者的OspA、OpsC和DbpA人单克隆抗体（HuMAbs）文库，并对HuMAbs进行与保护性免疫相关的功能活性表征。还将研究抗体与人类宿主抗原的交叉反应性，因为先前的研究揭示了对病原体的某些组分的抗体反应与莱姆病相关的衰弱性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。