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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Integrated single-cell analysis revealed immune dynamics during Ad5-nCoV immunization
Qiqi Cao,Shipo Wu,Chuan-Le Xiao,Shuzhen Chen,Xiangyang Chi,Xiuliang Cui,Hao Tang,Wenru Su,Yingfeng Zheng,Jiayong Zhong,Zhaomin Li,Fang Li,Haijia Chen,Lihua Hou,Hongyang Wang,Hongyang Wang,Wen Wen +16 more
TL;DR: Wang et al. as discussed by the authors performed scRNA/V(D)J-seq on peripheral blood mononuclear cells from four COVID-19 vaccine trial participants longitudinally during immunization, revealing enhanced cellular immunity with concerted and cell type-specific IFN responses as well as boosted humoral immunity with SARS-CoV-2-specific antibodies.
Journal ArticleDOI
A Rapid and Efficient Screening System for Neutralizing Antibodies and Its Application for SARS-CoV-2.
Xiaojian Han,Yingming Wang,Shenglong Li,Chao Hu,Tingting Li,Chenjian Gu,Kai Wang,Meiying Shen,Jianwei Wang,Jie Hu,Ruixin Wu,Song Mu,Fang Gong,Qian Chen,Fengxia Gao,Jingjing Huang,Yingyi Long,Feiyang Luo,Shuyi Song,Shunhua Long,Yanan Hao,Luo Li,Yang Wu,Wei Xu,Xia Cai,Qingzhu Gao,Guiji Zhang,Changlong He,Kun Deng,Li Du,Yaru Nai,Wang Wang,Youhua Xie,Di Qu,Ailong Huang,Ni Tang,Aishun Jin +36 more
TL;DR: In this article, a strategically screening method was proposed to obtain SARS-CoV-2 receptor-binding domain (RBD) specific neutralizing antibodies within 6 days, followed by additional 9 days for antibody production and function analysis.
Posted ContentDOI
A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection
Hejun Liu,Meng Yuan,Deli Huang,Sandhya Bangaru,Chang-Chun D Lee,Linghang Peng,Xueyong Zhu,David Nemazee,Marit J. van Gils,Rogier W. Sanders,Rogier W. Sanders,Hans-Christian Kornau,Hans-Christian Kornau,S. Momsen Reincke,S. Momsen Reincke,S. Momsen Reincke,Harald Prüss,Harald Prüss,Harald Prüss,Jakob Kreye,Nicholas C. Wu,Andrew B. Ward,Ian A. Wilson +22 more
TL;DR: The structural findings provide mechanistic insights into how this antibody can accommodate antigenic variation in these viruses and provide valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic coronaviruses.
Posted ContentDOI
One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening
Irene M. Francino Urdániz,Paul J. Steiner,Monica B Kirby,Fangzhu Zhao,Cyrus M. Haas,Shawn Barman,Emily R. Rhodes,Linghang Peng,Kayla G. Sprenger,Joseph G. Jardine,Timothy A. Whitehead +10 more
TL;DR: In this paper, a facile method to identify antibody escape mutants on SARS-CoV-2 S RBD was presented, which predominantly mapped to the periphery of the ACE2 recognition site with K417, D420, Y421, F486, and Q493 as notable hotspots.
Journal ArticleDOI
Bispecific VH/Fab antibodies targeting neutralizing and non-neutralizing Spike epitopes demonstrate enhanced potency against SARS-CoV-2.
Shion A. Lim,Josef A. Gramespacher,Katarina Pance,Nicholas J. Rettko,Paige Solomon,Jing Jin,Irene Lui,Susanna K. Elledge,Jia Liu,Colton J Bracken,Graham Simmons,Xin X. Zhou,Kevin Leung,James A. Wells +13 more
TL;DR: In this article, a bispecific antibody that combines both neutralizing and nonneutralizing epitopes on Spike-RBD is a promising and rapid engineering strategy to improve the potency of SARS-CoV-2 antibodies.
References
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Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2.
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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Davide F. Robbiani,Davide F. Robbiani,Christian Gaebler,Frauke Muecksch,Julio C. C. Lorenzi,Zijun Wang,Alice Cho,Marianna Agudelo,Christopher O. Barnes,Anna Gazumyan,Shlomo Finkin,Thomas Hagglof,Thiago Y. Oliveira,Charlotte Viant,Arlene Hurley,Hans Heinrich Hoffmann,Katrina G. Millard,Rhonda G. Kost,Melissa Cipolla,Kristie Gordon,Filippo Bianchini,Spencer T. Chen,Victor A. Ramos,Roshni Patel,Juan Dizon,Irina Shimeliovich,Pilar Mendoza,Harald Hartweger,Lilian Nogueira,Maggi Pack,Jill Horowitz,Fabian Schmidt,Yiska Weisblum,Eleftherios Michailidis,Alison W. Ashbrook,Eric Waltari,John E. Pak,Kathryn E. Huey-Tubman,Nicholas Koranda,Pauline R. Hoffman,Anthony P. West,Charles M. Rice,Theodora Hatziioannou,Pamela J. Bjorkman,Paul D. Bieniasz,Paul D. Bieniasz,Marina Caskey,Michel C. Nussenzweig,Michel C. Nussenzweig +48 more
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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