发热伴血小板减少综合征（SFTS）是由SFTS病毒（SFTSV）引起的急性高致死率传染病，现仍无有效的特异性药。我们前期结果及已有研究均提示，针对SFTSV表面糖蛋白（GN）的中和抗体可能有效对抗SFTS，但基于病人血清的抗体效价较低，难以满足研发需求。纳米抗体是骆驼源的新型功能性抗体片段，它分子量小、稳定性高、亲和力高而毒性和免疫原性较低，近来多用于抗体药研发。前期我们已合成GN并免疫骆驼，获得了针对SFTSV的高滴度抗血清并构建了噬菌体纳米抗体库。基于此，本项目拟研发抗SFTSV的纳米中和抗体，筛选高亲和力中和抗体并进行人源化改造，制备人源化纳米抗体（Nb-huFc），同时制备递呈Nb-huFc的腺相关病毒载体（AAV-Nb-huFc）以延长抗体半衰期；进一步拟应用已有的人源化小鼠评估Nb-huFc和AAV-Nb-huFc的体内疗效。本研究的完成将为SFTS治疗提供潜在的纳米抗体新药。

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel bunyavirus that recently emerged in China. Infection with SFTSV is associated with case-fatality rates of of 6.3%-30%, and neither antivirals nor vaccines are available at present. Our data also indicated that neutralizing antibodies specific for SFTSV envelope glycoprotein (GN) played a vital role in the survival of SFTS patient. Compared to traditional antibody, nanobody from camel presented unique features like high stability, high affinity and low immunogenicity，which contributed to its widely application in antibody drug development. Here, we plan to develop humanized nanobody drug in the therapy of SFTS with lack of effective drug and vaccine. GN protein was expressed to immunize camel, which was applied to screen nanobody via phage display library. Accordingly, humanized nanobody （Nb-huFc）and AAV-delivered Nb-huFc (AAV-NB-huFc) will be constructed and generated, which will be evaluated in SFTSV infected humanized mice model. One potential nanobody drug against SFTSV infection will be provided.