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A broad and potent neutralization epitope in SARS-related coronaviruses.
Yuan, Meng; Zhu, Xueyong; He, Wan-Ting; Zhou, Panpan; Kaku, Chengzi I; Capozzola, Tazio; Zhu, Connie Y; Yu, Xinye; Liu, Hejun; Yu, Wenli; Hua, Yuanzi; Tien, Henry; Peng, Linghang; Song, Ge; Cottrell, Christopher A; Schief, William R; Nemazee, David; Walker, Laura M; Andrabi, Raiees; Burton, Dennis R; Wilson, Ian A.
  • Yuan M; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
  • Zhu X; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
  • He WT; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.
  • Zhou P; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037.
  • Kaku CI; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037.
  • Capozzola T; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.
  • Zhu CY; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037.
  • Yu X; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037.
  • Liu H; Adimab, LLC, Lebanon, NH 03766.
  • Yu W; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.
  • Hua Y; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
  • Tien H; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
  • Peng L; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
  • Song G; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
  • Cottrell CA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
  • Schief WR; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
  • Nemazee D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.
  • Walker LM; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.
  • Andrabi R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.
  • Burton DR; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037.
  • Wilson IA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037.
Proc Natl Acad Sci U S A ; 119(29): e2205784119, 2022 07 19.
Article in English | MEDLINE | ID: covidwho-1908386
ABSTRACT
Many neutralizing antibodies (nAbs) elicited to ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through natural infection and vaccination have reduced effectiveness to SARS-CoV-2 variants. Here, we show that therapeutic antibody ADG20 is able to neutralize SARS-CoV-2 variants of concern (VOCs) including Omicron (B.1.1.529) as well as other SARS-related coronaviruses. We delineate the structural basis of this relatively escape-resistant epitope that extends from one end of the receptor binding site (RBS) into the highly conserved CR3022 site. ADG20 can then benefit from high potency through direct competition with ACE2 in the more variable RBS and interaction with the more highly conserved CR3022 site. Importantly, antibodies that are able to target this site generally neutralize a broad range of VOCs, albeit with reduced potency against Omicron. Thus, this conserved and vulnerable site can be exploited for the design of universal vaccines and therapeutic antibodies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal / Antibodies, Viral Topics: Vaccines / Variants Limits: Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal / Antibodies, Viral Topics: Vaccines / Variants Limits: Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article