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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Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display
Shiho Tanaka,C. Anders Olson,Christopher O. Barnes,Wendy Higashide,Marcos Gonzalez,Justin Taft,Arlan Richardson,Marta Martín-Fernández,Dusan Bogunovic,Priyanthi N. P. Gnanapragasam,Pamela J. Bjorkman,Patricia Spilman,Kayvan Niazi,Shahrooz Rabizadeh,Patrick Soon-Shiong +14 more
TL;DR: In this paper , Zhang et al. used mRNA display to identify a set of antibodies against SARS-CoV-2 spike (S) proteins and characterize the structures of nAbs that recognize epitopes in the S 1 subunit of the S glycoprotein.
Journal ArticleDOI
Combination Therapy With Casirivimab/Imdevimab and Remdesivir for Protracted SARS-CoV-2 Infection in B-cell-Depleted Patients
Maria Dioverti,David C. Gaston,C. Paul Morris,Carol Ann Huff,Tania Jain,Richard J. Jones,Viki Anders,Howard M. Lederman,Jacqueline Saunders,Heba H. Mostafa,Robin K. Avery +10 more
TL;DR: 3 B-cell-depleted patients with prolonged coronavirus disease 2019 infection who were successfully treated with a combination of casirivimab/imdevimab and remdesivir are presented.
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A human antibody of potent efficacy against SARS-CoV-2 in rhesus macaques showed strong blocking activity to B.1.351.
Chunyin Gu,Xiaodan Cao,Zongda Wang,Xue Hu,Yanfeng Yao,Yiwu Zhou,Peipei Liu,Xiaowu Liu,Ge Gao,Xiao Hu,Yecheng Zhang,Zhen Chen,Li Gao,Yun Peng,Fangfang Jia,Chao Shan,Li Yu,Kunpeng Liu,Nan Li,Weiwei Guo,Guoping Jiang,Juan Min,Jianjian Zhang,Lu Yang,Meng Shi,Tianquan Hou,Yanan Li,Weichen Liang,Guoqiao Lu,Congyi Yang,Yuting Wang,Kaiwen Xia,Zheng Xiao,Jianhua Xue,Xueyi Huang,Xin Chen,Haixia Ma,Donglin Song,Zhongzong Pan,Xueping Wang,Haibing Guo,Hong Liang,Zhiming Yuan,Wuxiang Guan,Su Jun Deng +44 more
TL;DR: In this paper, the authors identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform.
Posted ContentDOI
A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2
Li Zhang,Lei Cao,Gao Xingsu,Zheng Binyang,Yong-Qiang Deng,J Li,Rui Feng,Qian Bian,Xiling Guo,Nan Wang,Hong-Ying Qiu,Lei Wang,Zhen Cui,Qing Ye,Geng Chen,Kui-Kui Lu,Yin Chen,Yutao Chen,Hong-Xing Pan,Baoli Zhu,Cheng-Feng Qin,Xiangxi Wang,Fengcai Zhu +22 more
TL;DR: Results provide a proof-of-concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD, and results of competitive SPR assays and cryo-EM structures of Fabs bound to S unveil determinants of immunogenicity.
Journal ArticleDOI
Outpatient Treatment of SARS-CoV-2 Infection to Prevent COVID-19 Progression.
TL;DR: A wide variety of "repurposed" drugs explored for treatment of COVID-19 have had little or no benefit as discussed by the authors, however, intravenous monoclonal antibody (mAb) combinations have been authorized by the US FDA for emergency use (EUA) for outpatients with mild to moderate COVID19 including some active against emerging SARS-COV-2 variants of concern (VOC).
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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