抗体药物是生物制药领域的“潜力股”，在传染性疾病的治疗中具有重要作用。抗原特异记忆B细胞筛选及单细胞测序技术相结合，可迅速高效获得全人源高效中和抗体，申请人利用此技术已从寨卡、裂谷热康复病人分离出具有治疗前景的中和抗体，相应成果发表在Sci Transl Med与Nat Microbiol杂志。狂犬病毒（RABV）感染者出现神经症状后死亡率近100%，是严重威胁公共卫生与健康的病毒之一。RABV暴露后狂犬疫苗与单克隆中和抗体连用可有效降低发病率。RABV表面G蛋白是产生中和抗体的主要抗原。目前，申请人已获得基于VSV的重组狂犬病毒。本项目拟以重组狂犬病毒为“诱饵”，通过抗原特异记忆B细胞筛选及单细胞测序技术相结合从疫苗接种者体内分离靶向不同G抗原位点的抗体，再通过抗体重组与设计，形成覆盖所有RABV分离株的高效中和抗体，为全球、尤其是我国预防和消除RABV提供重要的抗体药物制剂。

Therapeutic antibodies play important roles in the treatment of infectious diseases. Isolation of human monoclonal antibodies (humAbs) from single human memory B cells by RT-PCR is a new strategy, which has been used to generate humAbs with therapeutic potentials targeting viruses and parasites. Using this strategy, the applicant also characterized several humAbs with high neutralizing activities and protection efficacies through a Zika patient and a Rift Valley fever patient. This work enables the applicant to publish papers on Science Translational Medicine (Cover) and Nature Microbiology, respectively. Rabies virus (RABV) is transmitted to humans by biting of dogs carrying the virus. Once the virus enters into the central nervous system (CNS), the fatality rate is approximately 100%. According to the recommendation of WHO, injection of the vaccines, together with the anti-RABV immunoglobulins for post-exposure prevention would effectively prevent the disease. G proteins on the envelope of RABV are the main antigens to stimulate the neutralizing antibodies. Currently, the applicant has constructed the recombinant RAVB using the backbone of Vesicular Stomatitis Virus (VSV, rVSV-RABV), which decreases the environment for manipulating the virus from biosafety lever (BSL)-3 to BSL-2. In this proposal, the applicant plans to use the rVSV-RABV as a bait, to screen the PBMCs from RABV-vaccinees. Then the genes encoding the variable regions from the sorted cells would be sequenced. Through recombination, the sequenced gene would be transformed to IgG1 forms for further evaluation, including antigens binding and neutralizing activities against rVSV-RABV. By reconstruction and recombination of multi-specific humAbs, if it is necessary, the applicant aims to design a humAb that could neutralize all the isolated RABV strains. This would provide important therapeutics for the prevention and control of rabies in humans and promote the process to eliminate rabies virus infection in China.