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

该合同支持流感血凝素衍生的人B细胞表位的鉴定，以及了解抗体介导的保护性免疫的基础研究，以及适用时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类样本的体外评估；3)提交表位数据、计算机软件和结构数据到免疫表位数据库和分析资源；4)研究与新发现的表位相关的抗体引发的保护或发病机制。该合同的目标是全面绘制与神经氨酸酶蛋白结合的人类保护性抗体的表位和流感血凝素的广泛保护位点。目的是鉴定保护性抗原和表位，长期目标是将数据转化为实验性疫苗研究中监测表位特异性反应的数据，合理设计基于结构的表位疫苗，并将分离的人单克隆抗体（mAb）作为开发工具，用于未来人类预防和治疗分子的开发。

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.