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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Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant.
Leonid Yurkovetskiy,Xue Wang,Kristen E. Pascal,Christopher Tomkins-Tinch,Christopher Tomkins-Tinch,Thomas Nyalile,Yetao Wang,Alina Baum,William E. Diehl,Ann Dauphin,Claudia Carbone,Kristen Veinotte,Shawn B. Egri,Stephen F. Schaffner,Stephen F. Schaffner,Jacob E. Lemieux,Jacob E. Lemieux,James B. Munro,Ashique Rafique,Abhi Barve,Pardis C. Sabeti,Christos A. Kyratsous,Natalya Dudkina,Kuang Shen,Jeremy Luban +24 more
TL;DR: D614G adopts conformations that make virion membrane fusion with the target cell membrane more probable but that D614G retains susceptibility to therapies that disrupt interaction of the SARS-CoV-2 S protein with the ACE2 receptor.
Journal ArticleDOI
The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens.
TL;DR: This review highlights and describes the recent progress that has been made in the biosynthesis, structure, function, and antigenicity of the SARS-CoV-2 S glycoprotein, aiming to provide valuable insights into the design and development ofThe S protein-based vaccines as well as therapeutics.
Posted ContentDOI
Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding.
Tyler N. Starr,Allison J. Greaney,Allison J. Greaney,Sarah K Hilton,Sarah K Hilton,Katharine H.D. Crawford,Katharine H.D. Crawford,Mary Jane Navarro,John E. Bowen,M. Alejandra Tortorici,Alexandra C. Walls,David Veesler,Jesse D. Bloom,Jesse D. Bloom,Jesse D. Bloom +14 more
TL;DR: An interactive visualization and open analysis pipeline is presented to facilitate use of the dataset for vaccine design and functional annotation of mutations observed during viral surveillance.
Journal ArticleDOI
Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo.
Alexandra Schäfer,Frauke Muecksch,Julio C. C. Lorenzi,Sarah R. Leist,Melissa Cipolla,Stylianos Bournazos,Fabian Schmidt,Rachel M. Maison,Anna Gazumyan,David R. Martinez,Ralph S. Baric,Davide F. Robbiani,Davide F. Robbiani,Theodora Hatziioannou,Jeffrey V. Ravetch,Paul D. Bieniasz,Paul D. Bieniasz,Richard A. Bowen,Michel C. Nussenzweig,Michel C. Nussenzweig,Timothy P. Sheahan +20 more
TL;DR: Human monoclonal antibody potency in vitro does not uniformly correlate with its in vivo neutralization of SARS-CoV-2, but antibody combinations show superior efficacy compared with single antibodies.
Journal ArticleDOI
Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2
Yufei Xiang,Sham Nambulli,Zhengyun Xiao,Heng Liu,Zhe Sang,Zhe Sang,W. Paul Duprex,Dina Schneidman-Duhovny,Cheng Zhang,Yi Shi,Yi Shi +10 more
TL;DR: A large repertoire of highly potent neutralizing nanobodies (Nbs) to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (RBD) is identified and a structure of one of the most potent Nbs in complex with the RBD is determined.
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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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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