Striking #Similarities between CDRs in Some #mAbs That Neutralize #COVID19 (ACS Med Chem Lett., abstract)

[Source: ACS Medicinal Chemistry Letters, full page: (LINK). Abstract, edited.]

Striking Similarities between CDRs in Some mAbs That Neutralize COVID-19

Tianxiong Mi and Kevin Burgess*

Cite this: ACS Med. Chem. Lett. 2020, XXXX, XXX, XXX-XXX

Publication Date: August 10, 2020  | DOI: https://doi.org/10.1021/acsmedchemlett.0c00409

Copyright © 2020 American Chemical Society

SUBJECTS: Immunology,

 

Abstract

Four of five different monoclonal antibodies (mAbs) that have been crystallized in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S) have remarkably similar primary and secondary loop structures at the heavy chain complementarity-determining regions (HCDR) 1 and 2. All these reports give a structural basis for the deceptively difficult problem of accurate peptidomimetic loop mimic design.

Keywords: SARS-CoV-2; COVID-19; Monoclonal antibodies.

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A neutralizing #human #antibody binds to the N-terminal domain of the #Spike protein of #SARS-CoV-2 (Science, abstract)

[Source: Science, full page: (LINK). Abstract, edited.]

A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2

Xiangyang Chi1,*, Renhong Yan2,*, Jun Zhang1,*, Guanying Zhang1, Yuanyuan Zhang2, Meng Hao1, Zhe Zhang1, Pengfei Fan1, Yunzhu Dong1, Yilong Yang1, Zhengshan Chen1, Yingying Guo2, Jinlong Zhang1, Yaning Li3, Xiaohong Song1, Yi Chen1, Lu Xia2, Ling Fu1, Lihua Hou1, Junjie Xu1, Changming Yu1, Jianmin Li1,†, Qiang Zhou2,†, Wei Chen1,†

1 Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China. 2 Key Laboratory of Structural Biology of Zhejiang Province, Institute of Biology, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China. 3 Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.

†Corresponding author. Email: cw0226@foxmail.com (W.C.); zhouqiang@westlake.edu.cn (Q.Z.); lijmqz@126.com (J.L.)

* These authors contributed equally to this work.

Science  07 Aug 2020: Vol. 369, Issue 6504, pp. 650-655 | DOI: 10.1126/science.abc6952

 

Hitting SARS-CoV-2 in a new spot

A key target for therapeutic antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the spike protein, a trimeric protein complex with each monomer comprising an S1 and an S2 domain that mediate binding to host cells and membrane fusion, respectively. In addition to the receptor binding domain (RBD), S1 has an N-terminal domain (NTD). In searching for neutralizing antibodies, there has been a focus on the RBD. Chi et al.isolated antibodies from 10 convalescent patients and identified an antibody that potently neutralizes the virus but does not bind the RBD. Cryo–electron microscopy revealed the epitope as the NTD. This NTD-targeting antibody may be useful to combine with RBD-targeting antibodies in therapeutic cocktails.

Science, this issue p. 650

 

Abstract

Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD. We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo–eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.

Keywords: SARS-CoV-2; COVID-19; Monoclonal antibodies.

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Fruitful neutralizing #antibody #pipeline brings hope to defeat #SARS-Cov-2 (Trends Pharmacol Sci., abstract)

[Source: Trends of Pharmacological Sciences, full page: (LINK). Abstract, edited.]

Fruitful neutralizing antibody pipeline brings hope to defeat SARS-Cov-2

Alex Renn, Ying Fu, Xin Hu, Matthew D. Hall, Anton Simeonov

Published: July 31, 2020 | DOI: https://doi.org/10.1016/j.tips.2020.07.004

 

Highlights

  • We are currently experiencing an explosion of antibody research against COVID-19 that include neutralizing antibodies against SARS-CoV-2 and therapeutic antibodies against COVID-19 associated hyperinflammation.
  • 8 neutralizing antibodies against SARS-CoV-2, LY-CoV555, JS016, REGN-COV2, TY027, BRII-196, BRII-198, CT-P59 and SCTA01, have now entered clinical trials (as of July 28th, 2020).
  • SARS-CoV-2 may develop resistance to neutralizing antibodies through accumulating spontaneous mutations.
  • The neutralizing antibodies also may show antibody-dependent enhancement (ADE) and amplify disease progression.

 

Abstract

With the recent spread of SARS-CoV-2 infecting over 16 million people worldwide as of July 28th, 2020, causing more than 650,000 deaths, there is a desperate need for therapeutic agents and vaccines. Building on the knowledge of the previous outbreaks of SARS-CoV-1 and MERS, the development of therapeutic antibodies and vaccines for COVID-19 is taking place at an unprecedented speed. In this review, the current efforts made toward developing neutralizing antibodies against COVID-19 are summarized. We also highlight the importance of having such a fruitful antibody development pipeline that will be helpful in combatting the potential escape plans of SARS-CoV-2 including somatic mutations and antibody-dependent enhancement (ADE).

Keywords: SARS-CoV-2; COVID-19; Monoclonal antibodies; Immunology.

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Structural basis for the #neutralization of #SARS-CoV-2 by an #antibody from a #convalescent patient (Nat Struct Mol Biol., abstract)

[Source: Nature Structural and Molecular Biology, full page: (LINK). Abstract, edited.]

Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

Daming Zhou, Helen M. E. Duyvesteyn, […] Kuan-Ying A. Huang

Nature Structural & Molecular Biology (2020)

 

Abstract

The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KD of 2 nM), and a 2.6-Å-resolution crystal structure of an RBD–EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues within this footprint are key to stabilizing the pre-fusion spike. Cryo-EM analyses of the pre-fusion spike incubated with EY6A Fab reveal a complex of the intact spike trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attached to Fab. EY6A binds what is probably a major neutralizing epitope, making it a candidate therapeutic for COVID-19.

Keywords: SARS-CoV-2; COVID-19; SARS-CoV; Monoclonal antibodies.

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Structural basis for #neutralization of #SARS-CoV-2 and SARS-CoV by a potent therapeutic #antibody (Science, abstract)

[Source: Science, full page: (LINK). Abstract, edited.]

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody

Zhe Lv1,8,*, Yong-Qiang Deng2,*, Qing Ye2,*, Lei Cao1,*, Chun-Yun Sun3,*, Changfa Fan4,*, Weijin Huang5, Shihui Sun2, Yao Sun1, Ling Zhu1, Qi Chen2, Nan Wang1,8, Jianhui Nie5, Zhen Cui1,8, Dandan Zhu1, Neil Shaw1, Xiao-Feng Li2, Qianqian Li5, Liangzhi Xie3,6,7,†, Youchun Wang5,†, Zihe Rao1,†, Cheng-Feng Qin2,†, Xiangxi Wang1,8,†

1 CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. 2 State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China. 3 Beijing Protein and Antibody R&D Engineering Center, Sinocelltech Ltd., Beijing 100176, China. 4 Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China. 5 Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China. 6 Beijing Antibody Research Key Laboratory, Sino Biological Inc., Building 9, Jing Dong Bei Technology Park, No.18 Ke Chuang 10th St, BDA, Beijing, 100176, China. 7 Cell Culture Engineering Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China. 8 University of Chinese Academy of Sciences, Beijing 100049, China.

†Corresponding author. Email: xiangxi@ibp.ac.cn (X.W.); qincf@bmi.ac.cn (C.-F.Q.); wangyc@nifdc.org.cn (Y.W.); liangzhi@yahoo.com (L.X.); raozh@tsinghua.edu.cn (Z.R.)

* These authors contributed equally to this work.

Science  23 Jul 2020: eabc5881 | DOI: 10.1126/science.abc5881

 

Abstract

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.

Keywords: SARS-CoV-2; COVID-19; SARS-CoV; Monoclonal antibodies.

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Potent neutralizing #antibodies directed to multiple #epitopes on #SARS-CoV-2 #spike (Nature, abstract)

[Source: Nature, full page: (LINK). Abstract, edited.]

This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike

Lihong Liu, Pengfei Wang, Manoj S. Nair, Jian Yu, Micah Rapp, Qian Wang, Yang Luo, Jasper F-W. Chan, Vincent Sahi, Amir Figueroa, Xinzheng V. Guo, Gabriele Cerutti, Jude Bimela, Jason Gorman, Tongqing Zhou, Zhiwei Chen, Kwok-Yung Yuen, Peter D. Kwong, Joseph G. Sodroski, Michael T. Yin, Zizhang Sheng, Yaoxing Huang, Lawrence Shapiro & David D. Ho

Nature (2020)

 

Abstract

The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, “all RBD-down” conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.

Keywords: SARS-CoV-2; COVID-19; Monoclonal antibodies.

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#Monoclonal #antibodies for the S2 subunit of #spike of #SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2

Zhiqiang Zheng1,2  , Vanessa Marthe Monteil3,4 , Sebastian Maurer-Stroh5,6,7 , Chow Wenn Yew8 , Carol Leong8 , Nur Khairiah Mohd-Ismail1,2 , Suganya Cheyyatraivendran Arularasu1,2 , Vincent Tak Kwong Chow1 , Raymond Tzer Pin Lin7,9 , Ali Mirazimi3,4,10 , Wanjin Hong8 , Yee-Joo Tan1,2,8

Affiliations: 1 Infectious Diseases programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore; 2 Immunology programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore; 3 Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden; 4 Public Health Agency of Sweden, Stockholm, Sweden; 5 Bioinformatics Institute (BII), A*STAR (Agency for Science, Technology and Research), Singapore; 6 Department of Biological Sciences (DBS), National University of Singapore, Singapore; 7 National Public Health Laboratory (NPHL), National Centre for Infectious Diseases (NCID), Singapore; 8 Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore; 9 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore; 10 National Veterinary Institute, Uppsala, Sweden

Correspondence:  Yee-Joo Tan

Citation style for this article: Zheng Zhiqiang  , Monteil Vanessa Marthe , Maurer-Stroh Sebastian , Yew Chow Wenn , Leong Carol , Mohd-Ismail Nur Khairiah , Cheyyatraivendran Arularasu Suganya , Chow Vincent Tak Kwong , Lin Raymond Tzer Pin , Mirazimi Ali , Hong Wanjin , Tan Yee-Joo . Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2. Euro Surveill. 2020;25(28):pii=2000291. https://doi.org/10.2807/1560-7917.ES.2020.25.28.2000291

Received: 12 Mar 2020;   Accepted: 11 Jun 2020

 

Abstract

Background

A novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002–2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.

Aim

The cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed.

Methods

The SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein.

Results

An immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format.

Conclusion

The cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: SARS-CoV-2; SARS-CoV; Monoclonal antibodies.

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Potently neutralizing and protective #human #antibodies against #SARS-CoV-2 (Nature, abstract)

[Source: Nature, full page: (LINK). Abstract, edited.]

This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Potently neutralizing and protective human antibodies against SARS-CoV-2

Seth J. Zost, Pavlo Gilchuk, James Brett Case, Elad Binshtein, Rita E. Chen, Joseph P. Nkolola, Alexandra Schäfer, Joseph X. Reidy, Andrew Trivette, Rachel S. Nargi, Rachel E. Sutton, Naveenchandra Suryadevara, David R. Martinez, Lauren E. Williamson, Elaine C. Chen, Taylor Jones, Samuel Day, Luke Myers, Ahmed O. Hassan, Natasha M. Kafai, Emma S. Winkler, Julie M. Fox, Swathi Shrihari, Benjamin K. Mueller, Jens Meiler, Abishek Chandrashekar, Noe B. Mercado, James J. Steinhardt, Kuishu Ren, Yueh-Ming Loo, Nicole L. Kallewaard, Broc T. McCune, Shamus P. Keeler, Michael J. Holtzman, Dan H. Barouch, Lisa E. Gralinski, Ralph S. Baric, Larissa B. Thackray, Michael S. Diamond, Robert H. Carnahan & 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.

Keywords: SARS-CoV-2; COVID-19; Monoclonal antibodies; Animal models.

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Development of a #monoclonal #antibody‐based antigen capture #ELISA for #detection of #H7N9 subtype #avian #influenza virus (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

Development of a monoclonal antibody‐based antigen capture enzyme‐linked immunosorbent assay for detection of H7N9 subtype avian influenza virus

Fan Yang,  Yixin Xiao,  Fumin Liu,  Hangping Yao,  Nanping Wu,  Haibo Wu

First published: 10 July 2020 | DOI:  https://doi.org/10.1002/jmv.26292

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26292

 

Abstract

In order to establish a rapid detection method for H7N9 avian influenza virus (AIV), monoclonal antibodies (mAbs) against hemagglutinin (HA) of H7N9 were developed to establish an antigen capture enzyme‐linked immunosorbent assay (AC‐ELISA). AC‐ELISA achieved high specificity and sensitivity, with a detection limit of 3.9 ng/ml for H7N9 HA protein (A/Zhejiang/DTID‐ZJU01/2013), and 2‐2 HA unit/100 μl for live H7N9 AIV. The inter‐ and intra‐assay coefficient of variation was less than 10%. Compared with conventional virus isolation detection, the sensitivity and specificity were 94.96% and 88.24%, respectively. AC‐ELISA proved to be a rapid and practical technique for detection of H7N9 AIV.

This article is protected by copyright. All rights reserved.

Keywords: Avian Influenza; H7N9; Monoclonal antibodies; Diagnostic tests.

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Longitudinal #isolation of potent near-germline #SARS-CoV-2-neutralizing #antibodies from #COVID-19 patients (Cell, abstract)

[Source: Cell, full page: (LINK). Abstract, edited.]

Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients

Christoph Kreer, Matthias Zehner, Timm Weber, Meryem S. Ercanoglu, Lutz Gieselmann, Cornelius Rohde, Sandro Halwe, Michael Korenkov, Philipp Schommers, Kanika Vanshylla, Veronica Di Cristanziano, Hanna Janicki, Reinhild Brinker, Artem Ashurov, Verena Krähling, Alexandra Kupke, Hadas Cohen-Dvashi, Manuel Koch, Jan Mathis Eckert, Simone Lederer, Nico Pfeifer, Timo Wolf, Maria J.G.T. Vehreschild, Clemens Wendtner, Ron Diskin, Henning Gruell, Stephan Becker, Florian Klein

Open Access | Published: July 07, 2020 | DOI: https://doi.org/10.1016/j.cell.2020.06.044

 

Highlights

  • Isolation of highly potent SARS-CoV-2-neutralizing antibodies
  • Longitudinal sampling reveals early class-switched neutralizing response
  • SARS-CoV-2-reactive antibodies show little somatic mutation over time
  • Potential antibody precursor sequences identified in SARS-CoV-2-naïve individuals

 

Summary

The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and world economy. Since approved drugs and vaccines are not available, new options for COVID-19 treatment and prevention are highly demanded. To identify SARS-CoV-2 neutralizing antibodies, we analysed the antibody response of 12 COVID-19 patients from 8 to 69 days post diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days post diagnosis. Of these, 28 potently neutralized authentic SARS-CoV-2 (IC100 as low as 0.04 μg/ml), showing a broad spectrum of V genes and low levels of somatic mutations. Interestingly, potential precursors were identified in naïve B cell repertoires from 48 healthy individuals that were sampled before the COVID-19 pandemic. Our results demonstrate that SARS-CoV-2 neutralizing antibodies are readily generated from a diverse pool of precursors, fostering the hope of rapid induction of a protective immune response upon vaccination.

Accepted: June 26, 2020 – Received in revised form: June 19, 2020 – Received: June 2, 2020

Publication stage In Press Accepted Manuscript

Identification DOI: https://doi.org/10.1016/j.cell.2020.06.044

Copyright © 2020 The Author(s). Published by Elsevier Inc.

Keywords: SARS-CoV-2; COVID-19; Monoclonal antibodies.

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