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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E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil.
Patrícia Aline Gröhs Ferrareze,Vinícius Bonetti Franceschi,Amanda de Menezes Mayer,Gabriel Dickin Caldana,Ricardo Ariel Zimerman,Claudia Elizabeth Thompson,Claudia Elizabeth Thompson +6 more
TL;DR: In this article, the authors performed genomic and phylogenetic analyses of the E484K mutated genomes sequenced from Brazilian samples in 2020 and found that more than 40% of the sequenced genomes present the mutation.
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A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody.
Nicholas C. Wu,Meng Yuan,Sandhya Bangaru,Deli Huang,Xueyong Zhu,Chang-Chun D Lee,Hannah L. Turner,Linghang Peng,Linlin Yang,Dennis R. Burton,David Nemazee,Andrew B. Ward,Ian A. Wilson +12 more
TL;DR: In insights into antigenic variation and potential cross-neutralizing epitopes on SARS-like viruses, a single mutation P384A fully determines the affinity difference in CR3022.
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Three SARS-CoV-2 reinfection cases by the new Variant of Concern (VOC) P.1/501Y.V3
Felipe Gomes Naveca,Cristiano Fernandes da Costa,Valdinete Alves do Nascimento,Victor Costa de Souza,André de Lima Guerra Corado,Fernanda Nascimento,Ágatha Costa,Débora Duarte,George Silva,Matilde Mejía,Karina Pessoa,Luciana Márcia Gonçalves,Maria Júlia Brandão,Michele Silva de Jesus,Marineide Silva,Tirza Mattos,Ligia Fernandes Abdalla,João Hugo Abdalla Santos,Rubens Carmo Costa-Filho,Tsuyoshi Sekizuka,Kentaro Itokawa,Masanori Hashino,Makoto Kuroda,Marilda M. Siqueira,Gabriel Luz Wallau,Edson Delatorre,Tiago Gräf,Gonzalo Bello,Paola Cristina Resende +28 more
TL;DR: The present study provides the first evidence of the new VOC P.1.1 causing multiple reinfections during the second epidemic peak in the Amazonas state and suggests that reinfected individuals may have been infectious.
Journal ArticleDOI
SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains.
Peter Radvak,Hyung-Joon Kwon,Martina Kosikova,Uriel Ortega-Rodriguez,Ruoxuan Xiang,Je-Nie Phue,Rong-Fong Shen,James Rozzelle,Neeraj Kapoor,Taylor Rabara,Jeff Fairman,Hang Xie +11 more
TL;DR: In this paper, the authors demonstrate that B.1.7 and B.351 are 100-fold more lethal than the original SARS-CoV-2 bearing 614D.
Journal ArticleDOI
Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies.
Maxwell T. Finkelstein,Adam G. Mermelstein,Emma Parker Miller,Paul C. Seth,Erik-Stephane D. Stancofski,Daniela Fera +5 more
TL;DR: In this paper, the authors highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2.
References
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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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