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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A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma.
Craig Fenwick,Priscilla Turelli,Céline Pellaton,Alex Farina,Jérémy Campos,Charlène Raclot,Florence Pojer,Valeria Cagno,Valeria Cagno,Semira Gonseth Nusslé,Valérie D'Acremont,Valérie D'Acremont,Jan Fehr,Milo A. Puhan,Giuseppe Pantaleo,Giuseppe Pantaleo,Didier Trono +16 more
TL;DR: In this paper, a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor is presented.
Journal ArticleDOI
The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19.
TL;DR: In this paper, the authors put forth three principles of antibody therapy, namely, specificity, temporal, and quantitative principles, connoting that antibody efficacy requires the administration of specific antibody, given early in course of disease in sufficient amount.
Journal ArticleDOI
SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface.
Federico Bertoglio,Doris Meier,Nora Langreder,Stephan Steinke,Ulfert Rand,Luca Simonelli,Philip Alexander Heine,Rico Ballmann,Kai-Thomas Schneider,Kristian Daniel Ralph Roth,Maximilian Ruschig,Peggy Riese,Kathrin Eschke,Yeonsu Kim,Dorina Schäckermann,Mattia Pedotti,Philipp Kuhn,Susanne Zock-Emmenthal,Johannes Wöhrle,Normann Kilb,Tobias Herz,Marlies Becker,Martina Grasshoff,Esther Veronika Wenzel,Giulio Russo,Andrea Kröger,Linda Brunotte,Stephan Ludwig,Viola Fühner,Stefan Kramer,Stefan Dübel,Luca Varani,Günter Roth,Luka Cicin-Sain,Maren Schubert,Michael Hust +35 more
TL;DR: Bergoglio et al. as discussed by the authors used phage display to select anti-SARS-CoV-2 spike antibodies from the human naive antibody gene libraries HAL9/10 and subsequent identification of 309 unique fully human antibodies against S1.
Journal ArticleDOI
Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2.
Damir Bojadzic,Oscar Alcazar,Jinshui Chen,Sung Ting Chuang,Jose Manuel Condor Capcha,Lina A. Shehadeh,Peter Buchwald +6 more
TL;DR: In this paper, small-molecule inhibitors of protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and human ACE2 (hACE2), which acts as a ligand-receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are identified.
Journal ArticleDOI
A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope.
Laura A. VanBlargan,Lucas J. Adams,Zhuoming Liu,Rita E. Chen,Pavlo Gilchuk,Saravanan Raju,Brittany K. Smith,Haiyan Zhao,James Brett Case,Emma S. Winkler,Bradley Whitener,Lindsay Droit,Ishmael D. Aziati,Traci L. Bricker,Astha Joshi,Pei Yong Shi,Adrian Creanga,Amarendra Pegu,Scott A. Handley,David Wang,Adrianus C. M. Boon,James E. Crowe,Sean P. J. Whelan,Daved H. Fremont,Michael S. Diamond +24 more
TL;DR: In this paper, a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2).
References
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Journal ArticleDOI
Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2.
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.
Journal ArticleDOI
Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.
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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.
Journal ArticleDOI
Convergent antibody responses to SARS-CoV-2 in convalescent individuals.
Davide F. Robbiani,Davide F. Robbiani,Christian Gaebler,Frauke Muecksch,Julio C. C. Lorenzi,Zijun Wang,Alice Cho,Marianna Agudelo,Christopher O. Barnes,Anna Gazumyan,Shlomo Finkin,Thomas Hagglof,Thiago Y. Oliveira,Charlotte Viant,Arlene Hurley,Hans Heinrich Hoffmann,Katrina G. Millard,Rhonda G. Kost,Melissa Cipolla,Kristie Gordon,Filippo Bianchini,Spencer T. Chen,Victor A. Ramos,Roshni Patel,Juan Dizon,Irina Shimeliovich,Pilar Mendoza,Harald Hartweger,Lilian Nogueira,Maggi Pack,Jill Horowitz,Fabian Schmidt,Yiska Weisblum,Eleftherios Michailidis,Alison W. Ashbrook,Eric Waltari,John E. Pak,Kathryn E. Huey-Tubman,Nicholas Koranda,Pauline R. Hoffman,Anthony P. West,Charles M. Rice,Theodora Hatziioannou,Pamela J. Bjorkman,Paul D. Bieniasz,Paul D. Bieniasz,Marina Caskey,Michel C. Nussenzweig,Michel C. Nussenzweig +48 more
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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