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，并与基础研究相结合，以了解抗体介导的保护性免疫，并在适用时，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。该合同的目的是全面绘制与神经氨基酶蛋白结合的人类保护性抗体的表位，并绘制出流感黑谷蛋白的广泛保护位点。目的是识别保护性抗原和表位，其长期目标是翻译数据，以监测实验性疫苗研究中的表位特异性反应，基于结构的表位疫苗的合理设计以及使用孤立的人类单隆抗体（MAB）的使用（MAB）孤立的工具，将作为预言的发展工具作为预言，将其作为预测的未来，将其作为未来的人类和更属性的人类和更属性的人类分离。