Cell Reports (Oct 2021)
Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses
- Bailey B. Banach,
- Gabriele Cerutti,
- Ahmed S. Fahad,
- Chen-Hsiang Shen,
- Matheus Oliveira De Souza,
- Phinikoula S. Katsamba,
- Yaroslav Tsybovsky,
- Pengfei Wang,
- Manoj S. Nair,
- Yaoxing Huang,
- Irene M. Francino-Urdániz,
- Paul J. Steiner,
- Matías Gutiérrez-González,
- Lihong Liu,
- Sheila N. López Acevedo,
- Alexandra F. Nazzari,
- Jacy R. Wolfe,
- Yang Luo,
- Adam S. Olia,
- I-Ting Teng,
- Jian Yu,
- Tongqing Zhou,
- Eswar R. Reddem,
- Jude Bimela,
- Xiaoli Pan,
- Bharat Madan,
- Amy D. Laflin,
- Rajani Nimrania,
- Kwok-Yung Yuen,
- Timothy A. Whitehead,
- David D. Ho,
- Peter D. Kwong,
- Lawrence Shapiro,
- Brandon J. DeKosky
Affiliations
- Bailey B. Banach
- Bioengineering Graduate Program, University of Kansas, Lawrence, KS 66045, USA
- Gabriele Cerutti
- Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA
- Ahmed S. Fahad
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA
- Chen-Hsiang Shen
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Matheus Oliveira De Souza
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA
- Phinikoula S. Katsamba
- Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA
- Yaroslav Tsybovsky
- Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
- Pengfei Wang
- Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
- Manoj S. Nair
- Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
- Yaoxing Huang
- Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
- Irene M. Francino-Urdániz
- Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USA
- Paul J. Steiner
- Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USA
- Matías Gutiérrez-González
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA
- Lihong Liu
- Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
- Sheila N. López Acevedo
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA
- Alexandra F. Nazzari
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Jacy R. Wolfe
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA
- Yang Luo
- Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
- Adam S. Olia
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- I-Ting Teng
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Jian Yu
- 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
- Tongqing Zhou
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Eswar R. Reddem
- Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA
- Jude Bimela
- Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA
- Xiaoli Pan
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA
- Bharat Madan
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA
- Amy D. Laflin
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA
- Rajani Nimrania
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA
- Kwok-Yung Yuen
- 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 Administrative Region, China; Department of Clinical Microbiology and Infection Control, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Timothy A. Whitehead
- Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USA
- David D. Ho
- Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
- Peter D. Kwong
- 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
- Lawrence Shapiro
- 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, USA; Corresponding author
- Brandon J. DeKosky
- 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; Corresponding author
- Journal volume & issue
-
Vol. 37,
no. 1
p. 109771
Abstract
Summary: 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 heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light 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.
