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DOI	10.1126/science.abf4830
	Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody
	Garrett Rappazzo C.; Tse L.V.; Kaku C.I.; Wrapp D.; Sakharkar M.; Huang D.; Deveau L.M.; Yockachonis T.J.; Herbert A.S.; Battles M.B.; O’Brien C.M.; Brown M.E.; Geoghegan J.C.; Belk J.; Peng L.; Yang L.; Hou Y.; Scobey T.D.; Burton D.R.; Nemazee D.; Dye J.M.; Voss J.E.; Gunn B.M.; McLellan J.S.; Baric R.S.; Gralinski L.E.; Walker L.M.
发表日期	2021
ISSN	0036-8075
起始页码	823
结束页码	829
卷号	371 期号:6531
英文摘要	The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope that overlaps the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses. © 2021 American Association for the Advancement of Science. All rights reserved.
英文关键词	monoclonal antibody; ACE2 protein, human; coronavirus spike glycoprotein; epitope; immunoglobulin Fc fragment; monoclonal antibody; spike protein, SARS-CoV-2; virus antibody; antibody; biochemistry; bioengineering; chemical binding; COVID-19; epidemic; neutralization; pathology; severe acute respiratory syndrome; virus; Article; binding affinity; binding site; biophysics; coronavirus disease 2019; disease burden; drug efficacy; drug potency; homologous recombination; human; hydrophobicity; protein binding; Saccharomyces cerevisiae; Severe acute respiratory syndrome coronavirus 2; thermostability; viral clearance; virus neutralization; virus replication; virus titration; animal; antibody affinity; antibody combining site; Bagg albino mouse; Betacoronavirus; cell surface display; directed molecular evolution; genetics; immunology; metabolism; passive immunization; prevention and control; protein domain; protein engineering; SARS coronavirus; severe acute respiratory syndrome; SARS coronavirus; Angiotensin-Converting Enzyme 2; Animals; Antibodies, Monoclonal; Antibodies, Viral; Antibody Affinity; Betacoronavirus; Binding Sites; Binding Sites, Antibody; Broadly Neutralizing Antibodies; Cell Surface Display Techniques; COVID-19; Directed Molecular Evolution; Epitopes; Humans; Immunization, Passive; Immunoglobulin Fc Fragments; Mice, Inbred BALB C; Protein Domains; Protein Engineering; Receptors, Coronavirus; SARS Virus; SARS-CoV-2; Severe Acute Respiratory Syndrome; Spike Glycoprotein, Coronavirus
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/243781
作者单位	Adimab, LLC, Lebanon, NH 03766, United States; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, United States; Department of Immunology and Microbiology, Scripps Research Institute, San diego, CA 92037, United States; Paul G. Allen School of Global Animal Health, Washington State University, Pullman, WA 99164, United States; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, United States; Geneva Foundation, Tacoma, WA 98402, United States; IAVI Neutralizing Antibody Center, Scripps Research Institute, San diego, CA 92037, United States; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, San diego, CA 92037, United States; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139, United States; Departments of Microbiology and...
推荐引用方式 GB/T 7714	Garrett Rappazzo C.,Tse L.V.,Kaku C.I.,et al. Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody[J],2021,371(6531).
APA	Garrett Rappazzo C..,Tse L.V..,Kaku C.I..,Wrapp D..,Sakharkar M..,...&Walker L.M..(2021).Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.Science,371(6531).
MLA	Garrett Rappazzo C.,et al."Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody".Science 371.6531(2021).