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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Computational epitope map of SARS-CoV-2 spike protein.
Mateusz Sikora,Mateusz Sikora,Sören von Bülow,Florian Blanc,Michael Gecht,Roberto Covino,Roberto Covino,Gerhard Hummer,Gerhard Hummer +8 more
TL;DR: In this paper, the SARS-CoV2 spike (S) protein is mapped to steric accessibility, structural rigidity, sequence conservation, and generic antibody binding signatures.
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Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection
Farina Karim,Mohamed Ys Moosa,Bernadett I Gosnell,Cele Sandile,Jennifer Giandhari,Sureshnee Pillay,Houriiyah Tegally,Eduan Wilkinson,Emmanuel James San,Nokukhanya Msomi,Koleka Mlisana,Koleka Mlisana,Khadija Khan,Mallory Bernstein,Nithendra Manickchund Nithendra,Lavanya Singh,Upasana Ramphal,Willem A. Hanekom,Richard J Lessells,Richard J Lessells,Alex Sigal,Alex Sigal,Tulio de Oliveira,Tulio de Oliveira +23 more
TL;DR: In this article, a case of prolonged infection of SARS-CoV-2 in an individual with advanced HIV and antiretroviral treatment failure was presented, where the early emergence of the E484K substitution associated with escape from neutralizing antibodies, followed by other escape mutations and the N501Y substitution found in most variants of concern.
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Concurrent human antibody andTH1 type T-cell responses elicited by a COVID-19 RNA vaccine
Ugur Sahin,Alexander Muik,Evelyna Derhovanessian,Isabel Vogler,Lena M. Kranz,Mathias Vormehr,Alina Baum,Kristen E. Pascal,Jasmin Quandt,Daniel Maurus,Sebastian Brachtendorf,Verena L Loerks,Julian Sikorski,Rolf Hilker,Dirk Becker,Ann-Kathrin Eller,Jan Gruetzner,Carsten Boesler,Corinna Rosenbaum,Marie-Cristine Kuehnle,Ulrich Luxemburger,Alexandra Kemmer-Brueck,David J. Langer,Martin Bexon,Stefanie Bolte,Katalin Karikó,Tania Palanche,Boris Fischer,Armin Schultz,Pei Yong Shi,Camila R. Fontes-Garfias,John L. Perez,Kena A. Swanson,Jakob Loschko,Ingrid L. Scully,Mark Cutler,Warren Kalina,Christos A. Kyratsous,David A. Cooper,Philip R. Dormitzer,Kathrin U. Jansen,Oezlem Tuereci +41 more
TL;DR: The robust RBD-specific antibody, T-cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest multiple beneficial mechanisms with potential to protect against COVID-19.
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Neutralization of spike 69/70 deletion, E484K, and N501Y SARS-CoV-2 by BNT162b2 vaccine-elicited sera
Xuping Xie,Yang Liu,Jianying Liu,Xianwen Zhang,Jing Zou,Camila R. Fontes-Garfias,Hongjie Xia,Kena A. Swanson,Mark Cutler,David A. Cooper,Vineet D. Menachery,Scott C. Weaver,Philip R. Dormitzer,Pei Yong Shi +13 more
TL;DR: In this paper, three SARS-CoV-2 viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants were engineered.
Journal ArticleDOI
Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial.
Meagan P. O'Brien,Eduardo Forleo-Neto,Neena Sarkar,Flonza Isa,Peijie Hou,Kuo-Chen Chan,Bret J. Musser,Katharine J. Bar,Ruanne V. Barnabas,Dan H. Barouch,Myron S. Cohen,Christopher B. Hurt,Dale R. Burwen,Mary A. Marovich,Elizabeth R. Brown,Ingeborg Heirman,John D. Davis,Kenneth C. Turner,Divya Ramesh,Adnan Mahmood,Andrea T. Hooper,Jennifer D. Hamilton,Yun-Nam Kim,Lisa A. Purcell,Alina Baum,Christos A. Kyratsous,James P. Krainson,R. Pérez Pérez,Rizwana Mohseni,Bari Kowal,A. Thomas DiCioccio,Gregory P. Geba,Neil Stahl,Leah Lipsich,Ned S. Braunstein,G D Herman,George D. Yancopoulos,David M. Weinreich +37 more
TL;DR: Among asymptomatic SARS-CoV-2 RT-qPCR-positive individuals living with an infected household contact, treatment with subcutaneous casirivimab and imdevimab antibody combination vs placebo significantly reduced the incidence of symptomatic COVID-19 over 28 days.
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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