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Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.
Rappazzo, C Garrett; Tse, Longping V; Kaku, Chengzi I; Wrapp, Daniel; Sakharkar, Mrunal; Huang, Deli; Deveau, Laura M; Yockachonis, Thomas J; Herbert, Andrew S; Battles, Michael B; O'Brien, Cecilia M; Brown, Michael E; Geoghegan, James C; Belk, Jonathan; Peng, Linghang; Yang, Linlin; Hou, Yixuan; Scobey, Trevor D; Burton, Dennis R; Nemazee, David; Dye, John M; Voss, James E; Gunn, Bronwyn M; McLellan, Jason S; Baric, Ralph S; Gralinski, Lisa E; Walker, Laura M.
  • Rappazzo CG; Adimab, LLC, Lebanon, NH 03766, USA.
  • Tse LV; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Kaku CI; Adimab, LLC, Lebanon, NH 03766, USA.
  • Wrapp D; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Sakharkar M; Adimab, LLC, Lebanon, NH 03766, USA.
  • Huang D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Deveau LM; Adimab, LLC, Lebanon, NH 03766, USA.
  • Yockachonis TJ; Paul G. Allen School of Global Animal Health, Washington State University, Pullman, WA 99164, USA.
  • Herbert AS; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Battles MB; The Geneva Foundation, Tacoma, WA 98402, USA.
  • O'Brien CM; Adimab, LLC, Lebanon, NH 03766, USA.
  • Brown ME; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Geoghegan JC; The Geneva Foundation, Tacoma, WA 98402, USA.
  • Belk J; Adimab, LLC, Lebanon, NH 03766, USA.
  • Peng L; Adimab, LLC, Lebanon, NH 03766, USA.
  • Yang L; Adimab, LLC, Lebanon, NH 03766, USA.
  • Hou Y; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Scobey TD; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Burton DR; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Nemazee D; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Dye JM; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Voss JE; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Gunn BM; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • McLellan JS; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139, USA.
  • Baric RS; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Gralinski LE; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Walker LM; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Science ; 371(6531): 823-829, 2021 02 19.
Article in English | MEDLINE | ID: covidwho-1048643
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Betacoronavirus / Broadly Neutralizing Antibodies / SARS-CoV-2 / Antibodies, Monoclonal / Antibodies, Viral Type of study: Randomized controlled trials Topics: Variants Limits: Animals / Humans Language: English Journal: Science Year: 2021 Document Type: Article Affiliation country: Science.abf4830

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Betacoronavirus / Broadly Neutralizing Antibodies / SARS-CoV-2 / Antibodies, Monoclonal / Antibodies, Viral Type of study: Randomized controlled trials Topics: Variants Limits: Animals / Humans Language: English Journal: Science Year: 2021 Document Type: Article Affiliation country: Science.abf4830