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Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses.
Banach, Bailey B; Cerutti, Gabriele; Fahad, Ahmed S; Shen, Chen-Hsiang; Oliveira De Souza, Matheus; Katsamba, Phinikoula S; Tsybovsky, Yaroslav; Wang, Pengfei; Nair, Manoj S; Huang, Yaoxing; Francino-Urdániz, Irene M; Steiner, Paul J; Gutiérrez-González, Matías; Liu, Lihong; López Acevedo, Sheila N; Nazzari, Alexandra F; Wolfe, Jacy R; Luo, Yang; Olia, Adam S; Teng, I-Ting; Yu, Jian; Zhou, Tongqing; Reddem, Eswar R; Bimela, Jude; Pan, Xiaoli; Madan, Bharat; Laflin, Amy D; Nimrania, Rajani; Yuen, Kwok-Yung; Whitehead, Timothy A; Ho, David D; Kwong, Peter D; Shapiro, Lawrence; DeKosky, Brandon J.
  • Banach BB; Bioengineering Graduate Program, University of Kansas, Lawrence, KS 66045, USA.
  • Cerutti G; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
  • Fahad AS; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA.
  • Shen CH; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Oliveira De Souza M; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA.
  • Katsamba PS; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
  • Tsybovsky Y; Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
  • Wang P; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Nair MS; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Huang Y; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Francino-Urdániz IM; Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USA.
  • Steiner PJ; Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USA.
  • Gutiérrez-González M; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA.
  • Liu L; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • López Acevedo SN; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA.
  • Nazzari AF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wolfe JR; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA.
  • Luo Y; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Olia AS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Teng IT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yu J; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Reddem ER; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
  • Bimela J; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
  • Pan X; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA.
  • Madan B; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA.
  • Laflin AD; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA.
  • Nimrania R; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA.
  • Yuen KY; State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Microbiology, Queen Mart Hospital, Hong Kong Special Administr
  • Whitehead TA; Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USA.
  • Ho DD; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Kwong PD; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Shapiro L; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY,
  • DeKosky BJ; Bioengineering Graduate Program, University of Kansas, Lawrence, KS 66045, USA; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA; Department of Chemical Engineering, University of Kansas, Lawrence, KS 66045, USA. Electronic address: dekosky@ku.edu.
Cell Rep ; 37(1): 109771, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1439919
Preprint
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ABSTRACT
Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavylight pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavylight class sequence signatures and determine antibody precursor prevalence to be ∼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal Type of study: Prognostic study / Risk factors Limits: Aged / Animals / Humans / Male Language: English Journal: Cell Rep Year: 2021 Document Type: Article Affiliation country: J.celrep.2021.109771

Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal Type of study: Prognostic study / Risk factors Limits: Aged / Animals / Humans / Male Language: English Journal: Cell Rep Year: 2021 Document Type: Article Affiliation country: J.celrep.2021.109771