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
Repeat subcutaneous administration of casirivimab and imdevimab in adults is well-tolerated and prevents the occurrence of COVID-19
Flonza Isa,Eduardo Forleo-Neto,J. Meyer,Wenjun Zheng,S.N. Rasmussen,Danielle Armas,Masaru H. Oshita,Cynthia Brinson,Steven D. Folkerth,Lori Faria,Ingeborg Heirman,Neena Sarkar,Bret J. Musser,Shikha Bansal,Meagan P. O'Brien,Kenneth C. Turner,Samit Ganguly,Adnan Mahmood,A. Dupljak,Andrea T. Hooper,Jennifer D. Hamilton,Yun-Nam Kim,Bari Kowal,Yuhwen Soo,Gregory P. Geba,Leah Lipsich,Ned S. Braunstein,George D. Yancopoulos,David M. Weinreich,Gary A. Herman +29 more
TL;DR: A phase 1, double-blind, placebo-controlled trial was conducted to evaluate the safety, tolerability, and exploratory efficacy of repeat monthly doses of subcutaneous (SC) casirivimab and imdevimab (CAS+IMD) in uninfected adult volunteers as discussed by the authors .
Journal ArticleDOI
SARS-COV-2 spike binding to ACE2 in living cells monitored by TR-FRET.
Emily the Criminal,Erika Cecon,Matilda Burridge,Longxing Cao,Lauren Carter,Rashmi Ravichandran,Julie Dam,Ralf Jockers +7 more
TL;DR: In this article, the authors developed an RBD-ACE2 binding assay that is based on time-resolved FRET, which reliably monitors the interaction in a physiologically relevant and cellular context.
Journal ArticleDOI
Enhanced virulence and waning vaccine-elicited antibodies account for breakthrough infections caused by SARS-CoV-2 delta and beyond
Hyung-Joon Kwon,Martina Kosikova,Weichun Tang,Uriel Ortega-Rodriguez,Peter Radvak,Ruoxuan Xiang,Kelly E. Mercer,Levan Muskhelishvili,Kelly J. Davis,Jerrold M. Ward,Ivan Kosik,Jaroslav Hollý,Insung Kang,Jonathan W. Yewdell,Ewan P. Plant,Wilbur H. Chen,Mallory Shriver,Robin S. Barnes,Marcela F. Pasetti,Bin Zhou,David E. Wentworth,Hang Xie +21 more
TL;DR: In this article , the authors investigated the factors responsible for SARS-CoV-2 breakthrough infections in a K18-hACE2 transgenic mouse model and found that enhanced virulence, greater immune evasion, and waning of vaccine-elicited protection account for the SARS CoV2 variants caused breakthrough infections.
Journal ArticleDOI
COVID-19 Clinical Trials Registered Worldwide for Drug Intervention: An Overview and Characteristic Analysis.
TL;DR: The designs of COVID-19 clinical drug trials have greatly improved in terms of the implementation of randomization and, particularly, blinding methods and the number of drug reuse, and hundreds of drugs have been used for efficacy screening.
Journal ArticleDOI
An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer
Naveenchandra Suryadevara,Andrea Shiakolas,Laura A. VanBlargan,Elad Binshtein,Rita E. Chen,James Brett Case,Kevin J Kramer,Erica Armstrong,Luke Myers,Andrew Trivette,Christopher Gainza,Rachel S. Nargi,Christopher N Selverian,Edgar Davidson,Benjamin J. Doranz,S. Diaz,Laura S. Handal,Robert H. Carnahan,Michael S. Diamond,Ivelin S. Georgiev,James E. Crowe +20 more
TL;DR: Insight is provided about antibody targeting of the S protein trimer interface region, suggesting this region may be a site of virus vulnerability in SARS-CoV-2, and a rare human antibody, COV2-3434, is discovered.
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