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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Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 RBD variants with a novel competitive multiplex assay
Ester Lopez,Ebene R. Haycroft,Amy Adair,Francesca L Mordant,Matthew T. O'Neill,Phillip Pymm,Phillip Pymm,Samuel J. Redmond,Nicholas A Gherardin,Nicholas A Gherardin,Adam K Whearley,Adam K Whearley,Jennifer A Juno,Kevin J. Selva,Samantha K Davis,Leigh Harty,Damian F. J. Purcell,Kanta Subbarao,Dale I. Godfrey,Dale I. Godfrey,Stephen J. Kent,Wai-Hong Tham,Wai-Hong Tham,Amy W. Chung +23 more
TL;DR: In this article, the authors developed a rapid, high-throughput, multiplex assay able to assess the inhibitory response of antibodies to 24 SARS-CoV-2 Receptor Binding Domain (RBD) natural variants simultaneously.
Journal ArticleDOI
Emerging SARS-CoV-2 variant B.1.1.7 reduces neutralisation activity of antibodies against wild-type SARS-CoV-2.
Katharina Müller,Philipp Girl,Andreas Giebl,Heiner von Buttlar,Gerhard Dobler,Joachim J. Bugert,Stefanie Gruetzner,Roman Wölfel +7 more
TL;DR: In this paper, the authors evaluated 96 serum samples from convalescent plasma donors collected before the first occurrence of B.1.7 and tested their neutralising effect on wild-type SARS-CoV-2 and B. 1.7.
Journal ArticleDOI
Generation and utility of a single-chain fragment variable monoclonal antibody platform against a baculovirus expressed recombinant receptor binding domain of SARS-CoV-2 spike protein
TL;DR: In this paper , a recombinant single-chain fragment variable (scFv) was used as a monoclonal antibody (MAb) platform targeting the receptor binding domain (RBD) of Spike protein of SARS-CoV-2.
Journal ArticleDOI
Novel Monoclonal Antibodies and Recombined Antibodies Against Variant SARS-CoV-2.
Jiajia Xie,Chengchao Ding,Jun He,Yuqing Zhang,Shuangshuang Ni,Xiangyu Zhang,Qingqing Chen,Jing Wang,Lina Huang,Hongliang He,Wenting Li,Huan Ma,Tengchuan Jin,Siping Zhang,Yong Gao +14 more
TL;DR: In this paper, two SARS-CoV-2 neutralizing antibodies (nAbs) were identified from convalescent COVID-19 patients and compared with nine nAbs that were reconstructed by using published data, and revealed that even though these two nAbs shared targeting epitopes on spike protein, they were different from any of the nine nabs.
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Inhibition of major histocompatibility complex-I antigen presentation by sarbecovirus ORF7a proteins
Fengwen Zhang,Trinity Zang,Eva M. Stevenson,Xiao Lei,Dennis C Copertino,Talia M. Mota,Julie Boucau,Wilfredo F. Garcia-Beltran,R. Brad Jones,Paul D. Bieniasz +9 more
TL;DR: SARS-CoV-2 ORF7a physically associated with the MHC-I heavy chain and inhibited the presentation of expressed antigen to CD8+ T-cells and a single-amino acid at position 59 (T/F) that is variable among sarbecovirus ORf7a proteins governed the difference in M HC-I downregulating activity.
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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