A neutralizing-protective supersite of human monoclonal antibodies for yellow fever virus

查看全文 作　　者：Yan [1]Li;Zhihai [2]Chen;Lili [1]Wu;Lianpan [1,3,4]Dai;Jianxun [1,3]Qi;Yan [1]Chai;Shihua [1]Li;Qihui [1]Wang;Zhou [1]Tong;Sufang [1]Ma;Xiaomin [1]Duan;Shuning [5]Ren;Rui [2]Song;Mifang [6]Liang;Wenjun [1]Liu;Jinghua [1,3]Yan;George [1,3,6,7]F.Gao

机构地区：[1]CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China;[2]Center of Infectious Disease,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China;[3]Savaid Medical School,University of Chinese Academy of Sciences,Beijing 101408,China;[4]Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine,Hainan Medical University,Haikou,Hainan 571199,China;[5]College of Veterinary Medicine,China Agricultural University,Beijing 100193,China;[6]National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention(China CDC),Beijing 102206,China;[7]Research Network of Immunity and Health,Beijing Institutes of Life Science,Chinese Academy of Sciences,Beijing 100101,China

出　　处：《The Innovation》索引2022年第3卷第6期,共9页

基　　金：Y.Chen and Z.Yang(Institute of Biophysics,CAS)for technical help with Biacore T100 and Octet RED96,and J.Jia(Institute of Biophysics,CAS)and T.Zhao(Institute of Microbiology,CAS)for technical support during BD FACSAria III and Caliburmanipulation;X.Lu(Tianjin Institute of Industrial Biotechnology,CAS)for providing pET 21a-YFV-sE plasmid.This work was supported by the National Key R&D Program of China(2021YFA1300803,2021YFC2300200);Strategic Priority Research Program of the Chinese Academy of Sciences(grant nos.XDB29040201,XDB37030204);National Natural Science Foundation of China(grant nos.31970854,32090014,81830050,81991494).L.Dai is supported by Youth Innovation Promotion Association CAS(2018113). 摘　　要：The yellow fever virus(YFV)is a life-threatening human pathogen.Owing to the lack of available therapeutics,non-vaccinated individuals are at risk.Here,we isolated eight human monoclonal antibodies that neutralize YFV infection.Five recognized overlapping epitopes and exhibited potent neutralizing activity.Two(YD6 and YD73)were ultra-potent and conferred complete protection against the lethal challenge of YFV as both prophylactics and therapeutics in a mouse model.Crystal structures revealed that YD6 engaged the YFV envelope protein in both pre-and post-fusion states,suggesting viral inhibition by a“double-lock”mechanism.The recognition determinants for YD6 and YD73 are clustered at the premembrane(prM)-binding site.Notably,antibodies targeting this site were present in minute traces in YFV-infected individuals but contributed significantly to neutralization,suggesting a vulnerable supersite of YFV.We provide two promising candidates for immunotherapy against YFV,and the supersite represents an ideal target for epitope-based vaccine design. 关键词：ANTIBODIES protective MONOCLONAL

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A neutralizing-protective supersite of human monoclonal antibodies for yellow fever virus

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