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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Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail.
Arnaud Drouin,Marc W. Theberge,Sharon Y. Liu,Allison R. Smither,Shelby M. Flaherty,Mark Zeller,Gregory P. Geba,Peter Reynaud,W. Benjamin Rothwell,Alfred Luk,Di Tian,Matthew L. Boisen,Luis M. Branco,Kristian G. Andersen,James E. Robinson,Robert F. Garry,Dahlene N. Fusco +16 more
TL;DR: A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection as discussed by the authors.
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One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening.
Irene M. Francino-Urdaniz,Paul J. Steiner,Monica B Kirby,Fangzhu Zhao,Cyrus M. Haas,Shawn Barman,Emily R. Rhodes,Alison C. Leonard,Linghang Peng,Kayla G. Sprenger,Joseph G. Jardine,Timothy A. Whitehead +11 more
TL;DR: In this article, a rapid method was described to identify escape mutants for nAbs targeting the S receptor binding site. But the method was limited to five nAbs, including three from the public germline class VH3-53 elicited by COVID-19 infection.
Journal ArticleDOI
The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants
Sylvia Rothenberger,Daniel L. Hurdiss,M. Walser,Francesca Malvezzi,Jennifer Mayor,Sarah Ryter,Hector Taddei Moreno,Nicole Liechti,Andreas Bosshart,Chloe Iss,Valerie Calabro,Andreas Cornelius,Tanja Hospodarsch,Alexandra Neculcea,Thamar Looser,Anja Schlegel,Simon Fontaine,Denis Villemagne,Maria Paladino,Dieter Schiegg,Susanne Mangold,Christian Reichen,Filip Radom,Y Kaufmann,Doris Schaible,Iris Schlegel,Christof Zitt,Gabriel Sigrist,Marcel Straumann,Juliane Wolter,Marco Comby,Feyza Sacarcelik,Ieva Drulyte,Heyrhyoung Lyoo,Chunyan Wang,Wentao Li,Wenjuan Du,H. Kaspar Binz,R. Herrup,Sabrina Lusvarghi,Sabari Nath Neerukonda,Russell Vassell,Wei Wang,Julia Adler,Kathrin Eschke,Mariana Nascimento,Azza Abdelrahman Abdelgawad,Achim D. Gruber,Judy Bushe,Olivia Kershaw,Charles G. Knutson,Kamal Kumar Balavenkatraman,Krishnan Ramanathan,Emanuel Wyler,LG Teixeira Alves,Seth Lewis,Randall P. Watson,Micha A. Haeuptle,Alexander Zürcher,Keith Martyn Dawson,Daniel Steiner,Carol D. Weiss,Patrick Amstutz,Frank J. M. van Kuppeveld,Michael T. Stumpp,Berend Jan Bosch,Olivier B. Engler,Jakob Trimpert +67 more
TL;DR: In this article , ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency.
Journal ArticleDOI
Biparatopic sybodies neutralize SARS‐CoV‐2 variants of concern and mitigate drug resistance
Justin D. Walter,M. Scherer,Cedric A. J. Hutter,Alisa A. Garaeva,Iwan Zimmermann,Marianne Wyss,Jan Rheinberger,Y. Ruedin,J. Earp,Pascal Egloff,M. Sorgenfrei,Lea M. Hürlimann,I. Gonda,Gianmarco Meier,Sille Remm,S. Thavarasah,Geert van Geest,Rémy Bruggmann,Gert Zimmer,Dirk Jan Slotboom,Cristina Paulino,Philippe Plattet,Markus A. Seeger +22 more
TL;DR: This study illustrates the power of multivalency and biparatopic nanobody fusions for the potential development of therapeutic strategies that mitigate the emergence of new SARS‐CoV‐2 escape mutants.
Posted ContentDOI
An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19
Rappazzo Cg,Longping V. Tse,Chengzi I. Kaku,Daniel Wrapp,Mrunal Sakharkar,Deli Huang,Deveau Lm,Yockachonis Tj,Andrew S. Herbert,Michael B. Battles,Cecilia M. O’Brien,Michael E. Brown,James C. Geoghegan,Jonathan P. Belk,Linghang Peng,Linlin Yang,Trevor Scobey,Dennis R. Burton,David Nemazee,John M. Dye,James E. Voss,Bronwyn M. Gunn,Jason S. McLellan,Ralph S. Baric,Lisa E. Gralinski,Laura M. Walker +25 more
TL;DR: A directed evolution approach is employed to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency and one of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic Sarbecoviruses with remarkable potency.
References
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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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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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