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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BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans
Ugur Sahin,Alexander Muik,Isabel Vogler,Evelyna Derhovanessian,Lena M. Kranz,Mathias Vormehr,Jasmin Quandt,Nicole Bidmon,Alexander Ulges,Alina Baum,Kristen E. Pascal,Daniel Maurus,Sebastian Brachtendorf,Verena L Loerks,Julian Sikorski,Peter Koch,Rolf Hilker,Dirk Becker,Ann-Kathrin Eller,Jan Gruetzner,Manuel Tonigold,Carsten Boesler,Corinna Rosenbaum,Ludwig Heesen,Marie-Cristine Kuehnle,Asaf Poran,Jesse Z. Dong,Ulrich Luxemburger,Alexandra Kemmer-Brueck,David J. Langer,Martin Bexon,Stefanie Bolte,Tania Palanche,Armin Schultz,Sybille Baumann,Azita J. Mahiny,Gábor Boros,Jonas Reinholz,Gabor T Szabo,Katalin Karikó,Pei Yong Shi,Camila R. Fontes-Garfias,John L. Perez,Mark Cutler,David A. Cooper,Christos A. Kyratsous,Philip R. Dormitzer,Kathrin U. Jansen,Oezlem Tuereci +48 more
TL;DR: Vaccination with BNT162b2 at well tolerated doses elicits a combined adaptive humoral and cellular immune response, which together may contribute to protection against COVID-19.
Journal ArticleDOI
Learning the language of viral evolution and escape.
TL;DR: This article used machine learning algorithms originally developed for human natural language to identify escape mutations that preserve viral infectivity but cause a virus to look different to the immune system, akin to word changes that preserve a sentence's grammaticality but change its meaning.
Journal ArticleDOI
Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications.
Ioannis P. Trougakos,Kimon Stamatelopoulos,Evangelos Terpos,Ourania E. Tsitsilonis,Evmorfia Aivalioti,Dimitrios Paraskevis,Efstathios Kastritis,George N. Pavlakis,Meletios-Athanasios Dimopoulos +8 more
TL;DR: In this paper, the authors discuss SARS-CoV-2 life cycle and a number of approaches aiming to suppress viral infection rates or propagation; increase virus antigen presentation in order to activate a robust and durable adaptive immune response from the host, and/or mitigate the ARDS-related "cytokine storm" and collateral tissue damage that triggers the severe life-threatening complications of COVID-19.
Journal ArticleDOI
Effects of SARS-CoV-2 variants on vaccine efficacy and response strategies.
TL;DR: As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread, several variants have emerged as discussed by the authors, including B.1.7 and B.2.351.
Journal ArticleDOI
Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape.
Zhiqiang Ku,Xuping Xie,Edgar Davidson,Xiaohua Ye,Hang Su,Vineet D. Menachery,Yize Li,Zihao Yuan,Xianwen Zhang,Antonio E. Muruato,Ariadna Grinyo i Escuer,Breanna Tyrell,Kyle Doolan,Benjamin J. Doranz,Daniel Wrapp,Paul Bates,Jason S. McLellan,Susan R. Weiss,Ningyan Zhang,Pei Yong Shi,Zhiqiang An +20 more
TL;DR: In this paper, the critical residues in the receptor-binding domain (RBD) used by multiple neutralizing antibodies and cocktails were compared and identified a combination of two antibodies CoV2-06 and CoV 2-14 for preventing SARS-CoV-2 escape.
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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Convergent antibody responses to SARS-CoV-2 in convalescent individuals.
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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