Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses
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-...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2021-10-01
|
Series: | Cell Reports |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721012250 |
id |
doaj-eeb91ec1080042a7abf186e7a830013e |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses Cell Reports SARS-CoV-2 public antibody neutralization yeast display B-cell biotechnology |
author_facet |
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 |
author_sort |
Bailey B. Banach |
title |
Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses |
title_short |
Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses |
title_full |
Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses |
title_fullStr |
Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses |
title_full_unstemmed |
Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses |
title_sort |
paired heavy- and light-chain signatures contribute to potent sars-cov-2 neutralization in public antibody responses |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2021-10-01 |
description |
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. |
topic |
SARS-CoV-2 public antibody neutralization yeast display B-cell biotechnology |
url |
http://www.sciencedirect.com/science/article/pii/S2211124721012250 |
work_keys_str_mv |
AT baileybbanach pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT gabrielecerutti pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT ahmedsfahad pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT chenhsiangshen pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT matheusoliveiradesouza pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT phinikoulaskatsamba pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT yaroslavtsybovsky pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT pengfeiwang pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT manojsnair pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT yaoxinghuang pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT irenemfrancinourdaniz pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT pauljsteiner pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT matiasgutierrezgonzalez pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT lihongliu pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT sheilanlopezacevedo pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT alexandrafnazzari pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT jacyrwolfe pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT yangluo pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT adamsolia pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT itingteng pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT jianyu pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT tongqingzhou pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT eswarrreddem pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT judebimela pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT xiaolipan pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT bharatmadan pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT amydlaflin pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT rajaninimrania pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT kwokyungyuen pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT timothyawhitehead pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT daviddho pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT peterdkwong pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT lawrenceshapiro pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses AT brandonjdekosky pairedheavyandlightchainsignaturescontributetopotentsarscov2neutralizationinpublicantibodyresponses |
_version_ |
1716840021783216128 |
spelling |
doaj-eeb91ec1080042a7abf186e7a830013e2021-10-07T04:24:53ZengElsevierCell Reports2211-12472021-10-01371109771Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responsesBailey B. Banach0Gabriele Cerutti1Ahmed S. Fahad2Chen-Hsiang Shen3Matheus Oliveira De Souza4Phinikoula S. Katsamba5Yaroslav Tsybovsky6Pengfei Wang7Manoj S. Nair8Yaoxing Huang9Irene M. Francino-Urdániz10Paul J. Steiner11Matías Gutiérrez-González12Lihong Liu13Sheila N. López Acevedo14Alexandra F. Nazzari15Jacy R. Wolfe16Yang Luo17Adam S. Olia18I-Ting Teng19Jian Yu20Tongqing Zhou21Eswar R. Reddem22Jude Bimela23Xiaoli Pan24Bharat Madan25Amy D. Laflin26Rajani Nimrania27Kwok-Yung Yuen28Timothy A. Whitehead29David D. Ho30Peter D. Kwong31Lawrence Shapiro32Brandon J. DeKosky33Bioengineering Graduate Program, University of Kansas, Lawrence, KS 66045, USADepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USADepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USADepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USADepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USAElectron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USAAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USAAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USAAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USADepartment of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USADepartment of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USADepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USAAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USADepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USADepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USAAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USADepartment 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, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USADepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USADepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USADepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USADepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USADepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USADepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USAState 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, ChinaDepartment of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USAAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USADepartment 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, USADepartment 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 authorBioengineering 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124721012250SARS-CoV-2public antibodyneutralizationyeast displayB-cellbiotechnology |