呼吸道合胞病毒全人源化单克隆抗体制备及其机理研究

呼吸道合胞病毒(RSV)是世界范围内引起下呼吸道感染的重要病原体之一，且目前尚无有效预防和治疗RSV感染的药物。鉴于此，本项目拟采用新颖的记忆性B细胞（BMem）抗体技术制备基因多样性好、效率高、全人源化的RSV单克隆抗体并研究其作用机制。目前，本课题组已完成RSV表面G/F抗原蛋白生产且成功将其应用于后继RSV抗体检测；从RSV感染者全血中分离得到BMem，成功将其诱导为可分泌RSV抗体的阳性浆细胞并建立相应的重链/轻链基因库。后继实验，本研究拟从阳性库中筛选得到全人源化RSV单克隆抗体，通过体外和小鼠实验分析其亲和力、特异性、中和能力、病毒抑制能力和ADCC活性等指标从而揭示其抗病毒机理。本项目首次将BMem细胞抗体制备技术应用于RSV单克隆抗体的生产，具有很好的原创性，为抗RSV病毒感染药物的研发和理论研究提供研究模式和新的思路。

Respiratory syncytial virus (RSV) is an important pathogen that causes lower respiratory tract infections worldwide, and there is no effective prevention and treatment drugs for RSV infection now. In view of this, the present project intends to produce fully human monoclonal antibody with genetic diversity and high efficiency using B cell antibody technology and reveal its mechanisms, which will benefit the treatment of RSV. Till now, our group have finished the production of RSV surface protein G/F for the detection of RSV antibodies; isolated memory B cells (BMem) from whole blood of RSV infected patients and stimulated these BMem into RSV antibody- secreting plasma cells, and constructed the gene library of heavy / light chains of RSV antibody. In the future experiments, we will selected the positive antibody for RSV viruses and reveal its mechanisms by evaluating its affinity, specificity, neutralizing capacity, virus inhibition and ADCC capability. We first use the B cell antibody technology to produce RSV monoclonal antibody, and our original work will provide good research models and new ideas for the development and production of RSV-infected drugs.