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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In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape
Marco Pretti,Rômulo Gonçalves Galvani,Nicole de Miranda Scherer,Alessandro S. Farias,Mariana Boroni +4 more
TL;DR: In this paper , the authors predicted SARS-CoV-2-specific CD8+ T cell epitopes from the main variants of concern and their potential to trigger or hinder T cell response by using HLA binding and TCR reactivity in silico predictions.
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COVID-19: should we consider it as a septic shock? (The treatment of COVID-19 patients in the ICU).
TL;DR: In this article, a review aimed to analyze the currently available data on the treatment of COVID-19, specifically the most studied antiviral agents and therapies targeting the immune system including those that have been investigated in sepsis.
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SARS-CoV-2 spike protein arrested in the closed state induces potent neutralizing responses
George Carnell,Katarzyna A. Ciazynska,David A. Wells,Xiaoli Xiong,Ernest T Aguinam,Stephen H. McLaughlin,Donna L. Mallery,Soraya Ebrahimi,Lourdes Ceron-Gutierrez,Leo C. James,Rainer Doffinger,Jonathan L. Heeney,John A. G. Briggs +12 more
TL;DR: In this paper, the results of immunization in a mouse model using an S protein trimer that is arrested in the closed state to prevent exposure of the receptor binding site and therefore interaction with the receptor.
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Potent monoclonal antibodies neutralize Omicron sublineages and other SARS-CoV-2 variants
Zhaochun Chen,Peng Zhang,Yumiko Matsuoka,Yaroslav Tsybovsky,Kamille A. West,Celia Santos,Lisa F. Boyd,Hanh T. Nguyen,Anna Pomerenke,Tyler Stephens,Adam S. Olia,Bao Shan Zhang,Valeria De Giorgi,Michael R. Holbrook,Robin Gross,Elena Postnikova,Nicole L. Garza,Reed F. Johnson,David H. Margulies,Peter D. Kwong,Harvey J. Alter,Ursula J. Buchholz,Paolo Lusso,Patrizia Farci +23 more
TL;DR: In this paper , the authors reported the generation and characterization of two potent human monoclonal antibodies, NA8 and NE12, against the receptor-binding domain of the SARS-CoV-2 spike protein.
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ACE2 decoy receptor generated by high-throughput saturation mutagenesis efficiently neutralizes SARS-CoV-2 and its prevalent variants
Bolun Wang,Junxuan Zhao,Shuo Liu,Jingyuan Feng,Yufeng Luo,Xinyu He,Yanmin Wang,Feixiang Ge,Junyi Wang,Buqing Ye,Weijin Huang,Xiaochen Bo,Youchun Wang,Jianzhong Xi +13 more
TL;DR: A comprehensive mutational landscape of the effects of ACE2-PD point mutations on RBD-ACE2 binding is presented using a saturation mutagenesis approach based on microarray-based oligo synthesis and a single-cell screening assay.
References
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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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