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
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An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants
TL;DR: In this article , a human monoclonal antibody, 87G7, was proposed to achieve broad neutralization and protection against Omicron and other SARS-CoV-2 variants.
Posted ContentDOI
Molecular evolution and structural analyses of the spike glycoprotein from Brazilian SARS-CoV-2 genomes: the impact of the fixation of selected mutations
Patrícia Aline Gröhs Ferrareze,Ricardo Ariel Zimerman,Vinícius Bonetti Franceschi,Gabriel Dickin Caldana,Paulo A. Netz,Claudia Elizabeth Thompson,Claudia Elizabeth Thompson +6 more
TL;DR: In this paper, the effect of positively selected mutations fixed in the Brazilian SARS-CoV-2 lineages and to check for mutational evidence of coevolution was evaluated by estimating the binding affinity in the RBD-hACE2 complex.
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MG1141A as a Highly Potent Monoclonal Neutralizing Antibody Against SARS-CoV-2 Variants
Sua Lee,ShinA Jang,Jihoon Kang,Soo Bin Park,Young Woo Han,Nam Hyemi,Munkyung Kim,Jeewon Lee,Ki Joon Cho,Jeonghun Kim,Mi-Young Oh,Jihye Ryu,Jong Hyeon Seok,Yunhwa Kim,Jee-Boong Lee,Man-Seong Park,Yong Sung Kim,Hosun Park,Dong-Sik Kim +18 more
TL;DR: In this paper, a humanized monoclonal antibody, MG1141A, against the receptor-binding domain of the spike protein of SARS-CoV-2 was generated through traditional mouse immunization.
Journal ArticleDOI
It is never too late for a cocktail - Development and analytical characterization of fixed-dose antibody combinations.
TL;DR: In this article , the authors summarize the recent progress on antibody fixed-dose combinations with a focus on important considerations during drug development and the analytical toolbox for co-formulated mAbs.
Journal ArticleDOI
Neutralizing monoclonal antibodies against highly pathogenic coronaviruses
TL;DR: In this paper , the authors summarized the progress of developing neutralizing monoclonal antibodies against infection of SARS-CoV-2, SARS CoV, and MERS CoV and discussed their potential applications in prevention and treatment of COVID-19 and other human coronavirus diseases.
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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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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