Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies.
Alina Baum,Benjamin O. Fulton,Elzbieta Wloga,Richard Copin,Kristen E. Pascal,Vincenzo Russo,Stephanie Giordano,Kathryn Lanza,Nicole Negron,Min Ni,Yi Wei,Gurinder S. Atwal,Andrew J. Murphy,Neil Stahl,George D. Yancopoulos,Christos A. Kyratsous +15 more
TLDR
This work investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails.Abstract:
Antibodies targeting the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present a promising approach to combat the coronavirus disease 2019 (COVID-19) pandemic; however, concerns remain that mutations can yield antibody resistance. We investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants that have arisen in the human population. However, novel spike mutants rapidly appeared after in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization; such escape also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein. Escape mutants were not generated after treatment with a noncompeting antibody cocktail.read more
Citations
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Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants.
Chunyan Yi,Xiaoyu Sun,Yixiao Lin,Chenjian Gu,Longfei Ding,Xiao Lu,Zhuo Yang,Yaguang Zhang,Liyan Ma,Wangpeng Gu,Aidong Qu,Xu Zhou,Xiuling Li,Jianqing Xu,Zhiyang Ling,Youhua Xie,Hongzhou Lu,Bing Sun +17 more
TL;DR: In-depth maps of four antigenic sites of the RBD are comprehensively profiled and mapped the binding hot spots for a panel of RBD-specific monoclonal antibodies isolated from COVID-19 convalescents, especially dominant VH3-53/3–66 antibodies, which are valuable indicators of antigenic changes in the R BD.
Posted ContentDOI
SARS-CoV-2 evolution in animals suggests mechanisms for rapid variant selection
Laura Bashor,Roderick B. Gagne,Angela M. Bosco-Lauth,Richard A. Bowen,Mark D. Stenglein,Sue VandeWoude +5 more
TL;DR: In this paper, the authors compared variants of cell culture-expanded SARS-CoV-2 inoculum and virus recovered from four species following experimental exposure, and found that five nonsynonymous changes in nsp12, S, N and M genes were near fixation in the inoculum but reverted to wild-type sequences in RNA recovered from dogs, cats and hamsters within 1-3 days post-exposure.
Journal ArticleDOI
SARS-CoV-2 neutralizing human antibodies protect against lower respiratory tract disease in a hamster model.
Bart L. Haagmans,Danny Noack,Nisreen M.A. Okba,Wentao Li,Chunyan Wang,Theo M. Bestebroer,Rory D. de Vries,Sander Herfst,Dennis de Meulder,Elwin Verveer,Peter van Run,Mart M. Lamers,Bart J. A. Rijnders,Casper Rokx,Frank J. M. van Kuppeveld,Frank Grosveld,Dubravka Drabek,Corine H. Geurts van Kessel,Marion Koopmans,Berend Jan Bosch,Thijs Kuiken,Barry Rockx +21 more
TL;DR: In this paper, the authors show that prophylactic administration of high levels of neutralizing antibody, either monoclonal or from convalescent plasma, prevent severe SARS-CoV-2 pneumonia in a hamster model, and could be used as an alternative or complementary to other antiviral treatments for COVID-19.
Journal ArticleDOI
Overview of Neutralizing Antibodies and Their Potential in COVID-19
José Javier Morales-Núñez,José Francisco Muñoz-Valle,Paola Carolina Torres-Hernández,Jorge Hernández-Bello +3 more
TL;DR: In this article, neutralizing antibody (NAb) evaluations are useful for determination of individual or herd immunity against SARS-CoV-2, vaccine efficacy, and humoral protective response longevity, as well as supporting donor selection criteria for convalescent plasma therapy.
Journal ArticleDOI
Quantum leap of monoclonal antibody (mAb) discovery and development in the COVID-19 era.
TL;DR: The history of antibodies from the times of serum therapy to modern mAbs is retrace and how the current run for effective treatments against COVID-19 will lead to a quantum leap in scientific, technological and health care system innovation around mAb treatments for infectious diseases is laid out.
References
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TL;DR: Cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein of SARS-CoV-2 are presented, providing important insights into the molecular basis for coronavirus recognition and infection.
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TL;DR: The crystal structure of the C-terminal domain of SARS-CoV-2 (SARS- coV- 2-CTD) spike (S) protein in complex with human ACE2 (hACE2) is presented, which reveals a hACE2-binding mode similar overall to that observed for SARS -CoV.
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TL;DR: Most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity, and rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
Journal ArticleDOI
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.
Dora Pinto,Young-Jun Park,Martina Beltramello,Alexandra C. Walls,M. Alejandra Tortorici,M. Alejandra Tortorici,Siro Bianchi,Stefano Jaconi,Katja Culap,Fabrizia Zatta,Anna De Marco,Alessia Peter,Barbara Guarino,Roberto Spreafico,Elisabetta Cameroni,James Brett Case,Rita E. Chen,Colin Havenar-Daughton,Gyorgy Snell,Amalio Telenti,Herbert W. Virgin,Antonio Lanzavecchia,Michael S. Diamond,Katja Fink,David Veesler,Davide Corti +25 more
TL;DR: Several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which was identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS- coV) in 2003, and one antibody (named S309) potently neutralization, which may limit the emergence of neutralization-escape mutants.
Journal ArticleDOI
Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells.
Y Cao,Bin Su,Xianghua Guo,Wenjie Sun,Yong-Qiang Deng,Linlin Bao,Qinyu Zhu,Xu Zhang,Yinghui Zheng,Chenyang Geng,Xiaoran Chai,Runsheng He,Xiaofeng Li,Qi Lv,Hua Zhu,Wei Deng,Yanfeng Xu,Yanjun Wang,Luxin Qiao,Yafang Tan,Liyang Song,Guopeng Wang,Xiao-Xia Du,Ning Gao,Jiangning Liu,Junyu Xiao,Xiao-Dong Su,Zongmin Du,Yingmei Feng,Chuan Qin,Cheng-Feng Qin,Ronghua Jin,X. Sunney Xie +32 more
TL;DR: It is shown that human neutralizing antibodies could be efficiently discovered by high-throughput single B-cell sequencing in response to pandemic infectious diseases.
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