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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Spatiotemporal dissemination pattern of SARS-CoV-2 B1.1.28-derived lineages introduced into Uruguay across its southeastern border with Brazil.
Natalia Rego,Tamara Fernández-Calero,Ighor Arantes,Veronica Noya,Daiana Mir,Mariana Brandes,Juan Zanetti,Mailen Arleo,Emiliano Pereira,Tania Possi,Odhille Chappos,Lucia Bilbao,Natalia Reyes,Melissa Duquia,Matías Victoria,Pia Techera,Maria Jose Benitez-Galeano,Luciana Griffero,Mauricio Mendez,Belén González,Pablo Smircich,Rodney Colina,Cecilia Alonso,Gonzalo Bello,Lucía Spangenberg +24 more
TL;DR: In this article, the authors investigated the factors that fueled SARS-CoV-2 viral dynamics during the first epidemic wave in the country and recovered 84 whole viral genomes from patients diagnosed between November, 2020 and February, 2021 in Rocha.
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Ultrapotent and broad neutralization of SARS-CoV-2 variants by modular, tetravalent, bi-paratopic antibodies
Sachdev S. Sidhu,Omar Camarillo +1 more
TL;DR: The tetravalent diabody-Fc-Fab as discussed by the authors is a modular platform for rapid production of drug-grade nAbs with potencies and breadth of coverage that greatly exceed those of conventional bivalent IgGs.
Journal ArticleDOI
An antibody cocktail with broadened mutational resistance and effective protection against SARS-CoV-2
Chunyun Sun,Hang Chi,Fei Yuan,Jing Li,Ji Yang,Aihua Zheng,Fei Wang,Lingling Sun,Yanjing Zhang,Ping Hu,Lihua Jiao,Yong-Qiang Deng,Liangzhi Xie +12 more
TL;DR: In this article , a new cocktail composed of two highly potent neutralizing antibodies (HB27 and H89Y) was developed, whose binding epitope is different from those cocktails that received emergency use authorization.
Journal ArticleDOI
An overview of methods for the structural and functional mapping of epitopes recognized by anti-SARS-CoV-2 antibodies
TL;DR: The sequence and structures for common neutralizing and non-neutralizing epitopes on the Spike protein are described as determined by X-ray crystallography, electron microscopy and linear peptide epitope mapping, among other methods.
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ACE2-Targeting Monoclonal Antibody as Potent and Broad-Spectrum Coronavirus Blocker
Yuning Chen,Ya-Nan Zhang,Renhong Yan,Guifeng Wang,Yuanyuan Zhang,Zhe-Rui Zhang,Yaning Li,jianxia ou,Wendi Chu,Zhijuan Liang,yongmei wang,Yi-Li Chen,Ganjun Chen,Qi Wang,Qiang Zhou,Bo Zhang,Bo Zhang,Chunhe Wang +17 more
TL;DR: In this paper, a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS CoV-1, CoV2 mutant variants, B.1.7 and P.617, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 knock-in mice.
References
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Journal ArticleDOI
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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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Convergent antibody responses to SARS-CoV-2 in convalescent individuals.
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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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