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
More filters
Journal ArticleDOI
REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters
Alina Baum,Dharani Ajithdoss,Richard Copin,Anbo Zhou,Kathryn Lanza,Nicole Negron,Min Ni,Yi Wei,Kusha Mohammadi,Bret J Musser,Gurinder S. Atwal,Adelekan Oyejide,Yenny Goez-Gazi,John Dutton,Elizabeth Clemmons,Hilary M. Staples,Carmen Bartley,Benjamin Klaffke,Kendra J. Alfson,Michal Gazi,Olga Gonzalez,Edward J. Dick,Ricardo Carrion,Laurent Pessaint,Maciel Porto,Anthony L. Cook,Renita Brown,Vaneesha Ali,Jack Greenhouse,Tammy Taylor,Hanne Leth Andersen,Mark G. Lewis,Neil Stahl,Andrew J. Murphy,George D. Yancopoulos,Christos A. Kyratsous +35 more
TL;DR: It is demonstrated that REGN-COV-2 can greatly reduce virus load in the lower and upper airways and decrease virus-induced pathological sequelae when administered prophylactically or therapeutically in rhesus macaques and golden hamsters.
Journal ArticleDOI
Neutralizing monoclonal antibodies for treatment of COVID-19.
Peter C. Taylor,Andrew C. Adams,Matthew M. Hufford,Inmaculada de la Torre,Kevin L. Winthrop,Robert L. Gottlieb,Robert L. Gottlieb +6 more
TL;DR: In this article, neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials.
Journal ArticleDOI
Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2.
Kui K. Chan,Danielle Dorosky,Preeti Sharma,Shawn A. Abbasi,John M. Dye,David M. Kranz,Andrew S. Herbert,Erik Procko +7 more
TL;DR: A variant of ACE2 based on deep mutagenesis far outcompetes the natural receptor in binding the SARS-CoV-2 spike protein and gives ACE2 variants with affinities that rival those of monoclonal antibodies.
Journal ArticleDOI
BNT162b2 vaccine induces neutralizing antibodies and poly-specific 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 Lörks,Julian Sikorski,Peter Koch,Rolf Hilker,Dirk Becker,Ann Kathrin Eller,Jan Grützner,Manuel Tonigold,Carsten Boesler,Corinna Rosenbaum,Ludwig Heesen,Marie Cristine Kühnle,Asaf Poran,Jesse Z. Dong,Ulrich Luxemburger,Alexandra Kemmer-Brück,David J. Langer,Martin Bexon,Stefanie Bolte,Tania Palanche,Armin Schultz,Sybille Baumann,Azita J. Mahiny,Gábor Boros,Jonas Reinholz,Gábor Szabó,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,Özlem Türeci +48 more
TL;DR: BNT162b2, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA (mRNA) that encodes the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike glycoprotein (S) stabilized in the prefusion conformation, has demonstrated 95% efficacy in preventing coronavalirus disease-19 (COVID-19)1 as mentioned in this paper.
Journal ArticleDOI
Antibody evasion by the P.1 strain of SARS-CoV-2.
Wanwisa Dejnirattisai,D. Zhou,P Supasa,Chang Liu,Alexander J. Mentzer,Helen M. Ginn,Yuguang Zhao,Duyvesteyn Hme.,Aekkachai Tuekprakhon,R Nutalai,Beibei Wang,Cesar Lopez-Camacho,J Slon-Campos,Thomas S. Walter,Donal T. Skelly,S A Costa Clemens,Felipe Gomes Naveca,Valdinete Alves do Nascimento,Fabrícia F. Nascimento,C Fernandes da Costa,Paola Cristina Resende,Alex Pauvolid-Corrêa,Marilda M. Siqueira,Christina Dold,R Levin,Tao Dong,Andrew J. Pollard,Julian C. Knight,D W Crook,Teresa Lambe,Elizabeth A. Clutterbuck,S Bibi,Amy Flaxman,M Bittaye,Sandra Belij-Rammerstorfer,Sarah C. Gilbert,Miles W. Carroll,Paul Klenerman,E Barnes,Susanna Dunachie,Neil G. Paterson,Mark A. Williams,David R. Hall,Hulswit Rjg.,Thomas A. Bowden,Elizabeth E. Fry,Juthathip Mongkolsapaya,Juthathip Mongkolsapaya,Jingshan Ren,David I. Stuart,Gavin R. Screaton +50 more
TL;DR: In this paper, structural analysis of the ACE2 binding sites of the SARS-CoV-2 pandemic strain has been carried out and the authors show that the 222 light chain is able to largely restore neutralization potency to a major class of public antibodies.
References
More filters
Journal ArticleDOI
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.
Journal ArticleDOI
Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.
Qihui Wang,Yanfang Zhang,Lili Wu,Sheng Niu,Sheng Niu,Chunli Song,Chunli Song,Zengyuan Zhang,Guangwen Lu,Chengpeng Qiao,Yu Hu,Yu Hu,Kwok-Yung Yuen,Qisheng Wang,Huan Zhou,Jinghua Yan,Jianxun Qi +16 more
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.
Journal ArticleDOI
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.
Related Papers (5)
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
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