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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The SARS-CoV-2 spike reversibly samples an open-trimer conformation exposing novel epitopes
Shawn M. Costello,Sophie R. Shoemaker,Helen T. Hobbs,Annalee W. Nguyen,Ching-Lin Hsieh,Jennifer A. Maynard,Jason S. McLellan,John E. Pak,Susan Marqusee +8 more
TL;DR: In this paper, an alternative conformation of SARS-CoV-2 spike ectodomain modulated by temperature, binding, and sequence variants was uncovered. But the authors did not reveal the structure and function of this protein.
Journal ArticleDOI
Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy.
Kristian Daniel Ralph Roth,Esther Veronika Wenzel,Maximilian Ruschig,Stephan Steinke,Nora Langreder,Philip Alexander Heine,Kai-Thomas Schneider,Rico Ballmann,Viola Fühner,Philipp Kuhn,Thomas Schirrmann,André Frenzel,Stefan Dübel,Maren Schubert,Gustavo Marçal Schmidt Garcia Moreira,Federico Bertoglio,Giulio Russo,Michael Hust +17 more
TL;DR: An overview of phage display derived recombinant antibodies against bacterial, viral and eukaryotic pathogens, as well as microbial toxins, intended for diagnostic and therapeutic applications is presented in this paper.
Journal ArticleDOI
Reprogrammed CRISPR-Cas13b suppresses SARS-CoV-2 replication and circumvents its mutational escape through mismatch tolerance.
Mohamed Fareh,Mohamed Fareh,Wei Zhao,Wenxin Hu,Wenxin Hu,Joshua M. L. Casan,Joshua M. L. Casan,Amit Kumar,Amit Kumar,Jori Symons,Jennifer M. Zerbato,Danielle Fong,Ilia Voskoboinik,Ilia Voskoboinik,Paul G Ekert,Rajeev Rudraraju,Rajeev Rudraraju,Damian F. J. Purcell,Sharon R Lewin,Sharon R Lewin,Sharon R Lewin,Joseph A. Trapani,Joseph A. Trapani +22 more
TL;DR: In this paper, the authors employ genome-wide computational prediction and single-nucleotide resolution screening to reprogram CRISPR-Cas13b against SARS-CoV-2 genomic and subgenomic RNAs.
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Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants
Lingshu Wang,Tongqing Zhou,Yi Zhang,Eun Sung Yang,Chaim A. Schramm,Wei Shi,Amarendra Pegu,Olamide K. Oloninyi,Amy Ransier,Samuel Darko,Sandeep Narpala,Christian Hatcher,David R. Martinez,Yaroslav Tsybovsky,Emily Phung,Olubukola M. Abiona,Evan M. Cale,Lauren A. Chang,Kizzmekia S. Corbett,Anthony T. DiPiazza,Ingelise J. Gordon,Kwanyee Leung,Tracy Liu,Rosemarie D. Mason,Alexandra Nazzari,Laura Novik,Adam S. Olia,Tyler Stephens,Christopher D. Stringham,Chloe Adrienna Talana,I-Ting Teng,Danielle A. Wagner,Alicia T. Widge,Baoshan Zhang,Mario Roederer,Julie E. Ledgerwood,Tracy J. Ruckwardt,Martin R. Gaudinski,Ralph S. Baric,Barney S. Graham,Adrian B. McDermott,Daniel C. Douek,Peter D. Kwong,John R. Mascola,Nancy J. Sullivan,John Misasi +45 more
TL;DR: In this paper, the authors identify four receptor-binding domain targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 12 variants including the B.1.7 and B.351 VOCs.
Posted ContentDOI
REGN-COV2 antibody cocktail prevents and treats SARS-CoV-2 infection in rhesus macaques and hamsters
Alina Baum,Richard Copin,Dharani Ajithdoss,Anbo Zhou,Kathryn Lanza,Nicole Negron,Min Ni,Yi Wei,Gurinder S. Atwal,Adelekan Oyejide,Yenny Goez-Gazi,John Dutton,Elizabeth Clemmons,Hilary M. Staples,Carmen Bartley,Benjamin Klaffke,Kendra J. Alfson,Michal Gazi,Olga Gonzales,Edward J. Dick,Ricardo Carrion,Laurent Pessaint,Maciel Porto,Anthony L. Cook,Renita Brown,Vaneesha Ali,Jack Greenhouse,Tammy Taylor,Hanne Leth Andersen,Mark G. Lewis,Neil Stahl,Andrew J. Murphy,George D. Yancopoulos,Christos A. Kyratsous +33 more
TL;DR: It is demonstrated that REGN-COV2 can greatly reduce virus load in lower and upper airway and decrease virus induced pathological sequalae when administered prophylactically or therapeutically and this results provide evidence of the therapeutic potential of this antibody cocktail.
References
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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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