《BioRxiv,3月31日,Fully human single-domain antibodies against SARS-CoV-2》

  • 来源专题:COVID-19科研动态监测
  • 编译者: zhangmin
  • 发布时间:2020-04-01
  • Fully human single-domain antibodies against SARS-CoV-2

    Yanling Wu, Cheng Li, Shuai Xia, Xiaolong Tian, Zhi Wang, Yu Kong, Chenjian Gu, Rong Zhang, Chao Tu, Youhua Xie, Lu Lu, Shibo Jiang, Tianlei Ying

    doi: https://doi.org/10.1101/2020.03.30.015990

    Abstract

    The COVID-19 pandemic is spreading rapidly, highlighting the urgent need for an efficient approach to rapidly develop therapeutics and prophylactics against SARS-CoV-2. We describe here the development of a phage-displayed single-domain antibody library by grafting naive CDRs into framework regions of an identified human germline IGHV allele. This enabled the isolation of high-affinity single-domain antibodies of fully human origin. The panning using SARS-CoV-2 RBD and S1 as antigens resulted in the identification of antibodies targeting five types of neutralizing or non-neutralizing epitopes on SARS-CoV-2 RBD. These fully human single-domain antibodies bound specifically to SARS-CoV-2 RBD with subnanomolar to low nanomolar affinities.

    *注,本文为预印本论文手稿,是未经同行评审的初步报告,其观点仅供科研同行交流,并不是结论性内容,请使用者谨慎使用.

  • 原文来源:https://www.biorxiv.org/content/10.1101/2020.03.30.015990v1
相关报告
  • 《CELL,5月5日,Identification of human single-domain antibodies against SARS-CoV-2》

    • 来源专题:COVID-19科研动态监测
    • 编译者:xuwenwhlib
    • 发布时间:2020-05-05
    • Identification of human single-domain antibodies againstSARS-CoV-2 Yanling Wu,Cheng Li,Shuai Xia,Xiaolong Tian,Yu Kong,Zhi Wang,Chenjian Gu,Rong Zhang,Chao Tu,2 Youhua Xie,1 Zhenlin Yang,3 Lu Lu,1Shibo Jiang,Tianlei Ying1,4 5 * SUMMARY The worldwide spread of COVID-19 highlights the need for an efficient approach torapidly develop therapeutics and prophylactics against SARS-CoV-2. TheSARS-CoV-2 spike protein, containing the receptor-binding domain (RBD) and S1subunit involved in receptor engagement, is a potential therapeutic target. We describethe development of a phage-displayed single-domain antibody library by graftingnaïve complementarity-determining regions (CDRs) into framework regions of ahuman germline immunoglobulin heavy chain variable region (IGHV) allele. Panningthis library against SARS-CoV-2 RBD and S1 subunit identified fully humansingle-domain antibodies targeting five distinct epitopes on SARS-CoV-2 RBD withsubnanomolar to low nanomolar affinities. Some of these antibodies neutralizeSARS-CoV-2 by targeting a cryptic epitope located in the spike trimeric interfaCollectively, this work presents a versatile platform for rapid antibody isolation andidentifies promising therapeutic anti-SARS-CoV-2 antibodies as well as the diverseimmogneic profile of the spike protein
  • 《Nature,7月15日,Potently neutralizing and protective human antibodies against SARS-CoV-2》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-07-28
    • Potently neutralizing and protective human antibodies against SARS-CoV-2 Seth J. Zost, Pavlo Gilchuk, […]James E. Crowe Jr Nature (2020) Abstract The COVID-19 pandemic is a major threat to global health1 for which there are limited medical countermeasures2,3. Moreover, we currently lack a thorough understanding of mechanisms of humoral immunity4. From a larger panel of human monoclonal antibodies (mAbs) targeting the spike (S) glycoprotein5, we identified several that exhibited potent neutralizing activity and fully blocked the receptor-binding domain of S (SRBD) from interacting with human ACE2 (hACE2). Competition-binding, structural, and functional studies allowed clustering of the mAbs into classes recognizing distinct epitopes on the SRBD as well as distinct conformational states of the S trimer. Potent neutralizing mAbs recognizing non-overlapping sites, COV2-2196 and COV2-2130, bound simultaneously to S and synergistically neutralized authentic SARS-CoV-2 virus. In two mouse models of SARS-CoV-2 infection, passive transfer of either COV2-2196 or COV2-2130 alone or a combination of both mAbs protected mice from weight loss and reduced viral burden and inflammation in the lung. In addition, passive transfer of each of two of the most potently ACE2 blocking mAbs (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on SRBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutics.