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Broadly neutralizing antibodies target the coronavirus fusion peptide.
Dacon, Cherrelle; Tucker, Courtney; Peng, Linghang; Lee, Chang-Chun D; Lin, Ting-Hui; Yuan, Meng; Cong, Yu; Wang, Lingshu; Purser, Lauren; Williams, Jazmean K; Pyo, Chul-Woo; Kosik, Ivan; Hu, Zhe; Zhao, Ming; Mohan, Divya; Cooper, Andrew J R; Peterson, Mary; Skinner, Jeff; Dixit, Saurabh; Kollins, Erin; Huzella, Louis; Perry, Donna; Byrum, Russell; Lembirik, Sanae; Drawbaugh, David; Eaton, Brett; Zhang, Yi; Yang, Eun Sung; Chen, Man; Leung, Kwanyee; Weinberg, Rona S; Pegu, Amarendra; Geraghty, Daniel E; Davidson, Edgar; Douagi, Iyadh; Moir, Susan; Yewdell, Jonathan W; Schmaljohn, Connie; Crompton, Peter D; Holbrook, Michael R; Nemazee, David; Mascola, John R; Wilson, Ian A; Tan, Joshua.
  • Dacon C; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Tucker C; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Peng L; Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
  • Lee CD; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Lin TH; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Yuan M; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Cong Y; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Wang L; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Purser L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Williams JK; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Pyo CW; Integral Molecular, Philadelphia, PA 19104, USA.
  • Kosik I; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Hu Z; Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhao M; Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Mohan D; Protein Chemistry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Cooper AJR; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Peterson M; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Skinner J; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Dixit S; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Kollins E; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Huzella L; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Perry D; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Byrum R; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Lembirik S; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Drawbaugh D; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Eaton B; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Zhang Y; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Yang ES; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chen M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Leung K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Weinberg RS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Pegu A; New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA.
  • Geraghty DE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Davidson E; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Douagi I; Integral Molecular, Philadelphia, PA 19104, USA.
  • Moir S; Flow Cytometry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yewdell JW; B Cell Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Schmaljohn C; Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Crompton PD; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Holbrook MR; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Nemazee D; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Mascola JR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Wilson IA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Tan J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Science ; 377(6607): 728-735, 2022 08 12.
Article in English | MEDLINE | ID: covidwho-1968212
ABSTRACT
The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. COV44-62 and COV44-79 broadly neutralize alpha- and betacoronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than receptor binding domain-specific antibodies. In crystal structures of COV44-62 and COV44-79 antigen-binding fragments with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine residue at the S2' cleavage site. COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings highlight the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Broadly Neutralizing Antibodies / SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal / Antibodies, Viral / Epitopes Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Humans Language: English Journal: Science Year: 2022 Document Type: Article Affiliation country: Science.abq3773

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Broadly Neutralizing Antibodies / SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal / Antibodies, Viral / Epitopes Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Humans Language: English Journal: Science Year: 2022 Document Type: Article Affiliation country: Science.abq3773