B-Cell Epitope Discovery and Mechanisms of Antibody Protection: Genetic and Structural Basis for Influenza Neutralization

B 细胞表位发现和抗体保护机制：流感中和的遗传和结构基础

• 批准号: 10903692
• 负责人: James E Crowe
• 金额: $ 64.56万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 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/10903692
• 关键词: Animals; Antibodies; Antibody Response; Antibody-mediated protection; Antigens; B-Lymphocyte Epitopes; Binding; Biological; Biological Assay; Complement; Computer software; Contracts; Coupled; Crystallography; Data; Databases; Deposition; Deuterium; Development; Electron Microscopy; Epitope Mapping; Epitopes; Evaluation; Future; Genetic; Goals; Human; Hydrogen; Immune; In Vitro; Influenza; Influenza Hemagglutinin; Mass Spectrum Analysis; Mediating; Monitor; Mutagenesis; Neuraminidase; Pathogenesis; Pathologic; Phagocytosis; Proteins; Resources; Sampling; Site; Structure; Support Contracts; Testing; Therapeutic; Translating; Vaccines; Validation; antibody-dependent cell cytotoxicity; antibody-dependent cellular phagocytosis; human monoclonal antibodies; neutrophil; prophylactic; rational design; response; tool development; vaccine trial

This contract supports the identification of human B cell epitopes derived from influenza hemagglutinin, coupled with basic studies to understand protective immunity mediated by antibodies and, when applicable, 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. The goal of this contract is to comprehensively map the epitopes of human protective antibodies that bind to the neuraminidase protein and to broadly protective sites of influenza hemagglutinin. The purpose is to identify protective antigens and epitopes, with the long-term goal of translating the data for monitoring epitope-specific responses in experimental vaccine studies, rational design of structure-based epitope vaccines, and use of isolated human monoclonal antibodies (mAb) isolated as developmental tools for development future as prophylactic and therapeutic molecules in humans.

该合同支持鉴定源自流感血凝素的人类 B 细胞表位，并结合基础研究来了解抗体介导的保护性免疫，以及在适用时了解抗体反应的病理后果。里程碑包括 1) 表位鉴定； 2) 表位验证，必须包括使用人体样本进行体外评估； 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）帮助了解与新鉴定的表位相关的抗体引起的保护机制或发病机制的研究。该合同的目标是全面绘制人类保护性抗体的表位图​​谱，这些抗体与神经氨酸酶蛋白和流感血凝素的广泛保护位点结合。目的是识别保护性抗原和表位，长期目标是转化数据以监测实验疫苗研究中的表位特异性反应、合理设计基于结构的表位疫苗以及分离的人单克隆抗体（mAb）的使用分离作为开发工具，用于未来作为人类预防和治疗分子的开发。