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

• 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
• 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

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.

母奖项的目标是发现和验证表位，确定抗体对新鉴定的表位的作用机制，并将表位沉积到该机构的免疫表位数据库（IEDB.org）。承包商正在筛选从被诊断患有莱姆病（由病原体伯氏疏螺旋体引起）的患者收集的大量血清样本，以确定与预防莱姆病相关的抗体，以及可能导致莱姆病衰弱的慢性症状的抗体。在执行合同工作的过程中，他在莱姆病关节炎和莱姆病神经螺旋体病患者的血清中发现了两种诱导抗体的蛋白质。这些发现与我们对慢性莱姆病症状病理的理解有很强的相关性，并可能为疫苗的开发提供信息。合理设计莱姆病亚单位疫苗需要包括预防伯氏疏螺旋体感染的表位，但也应排除可能通过诱导致病性抗体反应而引起不良副作用的区域。目前还没有批准用于人类的疫苗。蜱虫数量继续增加，人类中蜱传疾病的发病率也相应增加。解决这一日益严重的公共卫生问题的能力取决于对了解人类对感染的反应的研究，并利用这些数据作为确定作为候选疫苗进行测试的保护性成分的线索。