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

蜱传疾病：B 细胞表位发现和抗体保护机制

基本信息

批准号：
10678249
负责人：
Nicholas J. Mantis
金额：
$ 112.33万
依托单位：
NYSDOH/HEALTH RESEARCH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-16 至 2023-09-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10678249
关键词：
Address Affinity Amino Acids Antibodies Antibody Response Antibody-mediated protection Area Award B-Lymphocyte Epitopes Binding Borrelia Infections Borrelia burgdorferi Chronic Collection Complement Complex Contractor Contracts Data Databases Deposition Deuterium Diagnosis Differentiation Antigens Epitope Mapping Epitopes Extracellular Matrix Goals Human Hydrogen Immune Immunoglobulin G Incidence Infection Lyme Arthritis Lyme Disease Lyme Neuroborreliosis Maps Mass Spectrum Analysis Membrane Proteins Mus Operon OspA protein Parents Pathogenicity Pathology Patients Peripheral Blood Mononuclear Cell Proteins Public Health Reagent Recombinants Reporting Research Resistance Resolution Sampling Serum Structure Subunit Vaccines Surface Symptoms Testing Tick-Borne Diseases Vaccine Antigen Vaccines Validation Work X-Ray Crystallography base cross reactivity decorin binding protein A decorin binding protein B diagnostic biomarker flexibility human disease human monoclonal antibodies humanized mouse immunogenic immunoreactivity mouse model pathogen persistent symptom prevent protein B rational design response screening side effect tick population vaccine candidate vaccine development virtual

项目摘要

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.

父母奖的目的是表位发现和验证，确定新确定的表位抗体的作用机制，以及对表位置的沉积到该机构的免疫表位数据库（IEDB.org）中。承包商正在筛选大量由病原体Borlelia burgdorferi引起的诊断为莱姆病的患者收集的大量血清样品，以鉴定与莱姆病的保护相关的抗体，以及可能引起衰弱的抗体，可能引起衰弱的莱姆病症状。在执行合同工作的过程中，他确定了两种蛋白质，这些蛋白质会诱导莱姆关节炎症状和莱姆神经性疾病症状的血清中发现的抗体。这些发现与我们对慢性莱姆病症状的病理的理解有很强的意义，并可能为疫苗开发提供了信息。莱姆亚基疫苗的合理设计将需要包括预防漏漏感染的表位，但还应排除可能通过诱导致病性抗体反应引起不良副作用的区域。目前尚未批准人类的疫苗。随着人类tick虫疾病的相应增加，tick人口继续增加。解决这一不断增长的公共卫生问题的能力取决于研究人类对感染的反应，并将数据用作群集以识别受保护的成分作为候选疫苗的测试。