艾滋病是导致人体病毒持续性感染的重大传染病。抗病毒中和抗体在抑制病毒复制和缓解疾病进程中起着关键的作用。中和抗体在感染者体内产生的过程、结构和功能特点、识别表位的变化趋势以及与疾病进展的关系等是国际上研究的热点和难点。本课题立足我国艾滋病感染和艾滋病病毒的特点，利用创新型酵母抗原文库技术、单个B细胞分离抗体技术，B淋巴细胞免疫活化以及抗病毒中和能力的评估系统，重点研究：1）艾滋病持续感染过程中广谱中和活性抗体反应的特点，包括疾病进展过程中，血清/血浆多克隆抗体反应定性、定量的全景动态分析以及与疾病进展的关系；2）具有广谱中和活性单克隆抗体的分离、结构和功能研究；3）广谱中和活性抗体相关抗原表位的免疫原性研究等。这一研究将为解析抗艾滋病持续性感染的中和抗体免疫保护机制，为我们利用相关的保护性免疫特点，在国际上率先研发具我国自主知识产权的预防和治疗手段，提供关键的理论依据和技术支撑。

Human immunodeficiency virus type I (HIV-1) causes persistent infection in humans. Neutralizing antibodies (nAbs) play key roles in inhibiting viral replication and attenuating disease procession. Over the last several years, great progress has been made to dissect the intricate relationship between nAb and the virus, leading to the discovery of several broadly neutralizing monoclonal antibodies and their vulnerable targets on the virus. However, our understanding of nAb response in infected patients is far from complete. In particular, as HIV-1 strains circulating in China bearing unique genetic and phenotypic makeup, the nAb response in Chinese patients is likely to be different. Recently, our laboratory has developed and adapted comprehensive approaches to characterize nAb response in infected patients from both polyclonal and monoclonal perspectives. Armed with these approaches, we aim to study the following: 1) to characterize the dynamic features of antibody response in infected patients by qualitative and quantitative measurement of serum/plasma polyclonal antibody during disease progression; 2) to isolate and characterize the structure and function relationship of nAbs directly from infected patients; 3) to map the epitopes of isolated nAbs and based on which to rationally design and evaluate epitope-focused immunogens. We believe our proposed study will help us better understand the nAb response in infected patients and assist us in the design and development of more effective preventative and therapeutic measures against HIV-1 infection.