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SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike

View ORCID ProfileJenna J. Guthmiller, Olivia Stovicek, Jiaolong Wang, View ORCID ProfileSiriruk Changrob, Lei Li, View ORCID ProfilePeter Halfmann, Nai-Ying Zheng, Henry Utset, Christopher T. Stamper, View ORCID ProfileHaley L. Dugan, William D. Miller, Min Huang, Ya-Nan Dai, Christopher A. Nelson, View ORCID ProfilePaige D. Hall, Maud Jansen, Kumaran Shanmugarajah, Jessica S. Donington, Florian Krammer, Daved H. Fremont, View ORCID ProfileAndrzej Joachimiak, Yoshihiro Kawaoka, Vera Tesic, Maria Lucia Madariaga, Patrick C. Wilson
doi: https://doi.org/10.1101/2020.09.12.294066
Jenna J. Guthmiller
1Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
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  • ORCID record for Jenna J. Guthmiller
  • For correspondence: jguthmiller@uchicago.edu wilsonp@uchicago.edu
Olivia Stovicek
1Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
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Jiaolong Wang
1Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
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Siriruk Changrob
1Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
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Lei Li
1Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
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Peter Halfmann
2Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53711
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Nai-Ying Zheng
1Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
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Henry Utset
1Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
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Christopher T. Stamper
3Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
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Haley L. Dugan
3Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
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William D. Miller
4Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL 60637, USA
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Min Huang
1Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
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Ya-Nan Dai
5Department of Pathology and Immunology and Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, Washington University School of Medicine, St. Louis, MO 63110, USA
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Christopher A. Nelson
5Department of Pathology and Immunology and Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, Washington University School of Medicine, St. Louis, MO 63110, USA
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Paige D. Hall
5Department of Pathology and Immunology and Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, Washington University School of Medicine, St. Louis, MO 63110, USA
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Maud Jansen
6Department of Medicine, University of Chicago, Chicago, IL 60637, USA
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Kumaran Shanmugarajah
7Department of Surgery, University of Chicago, Chicago, IL 60637, USA
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Jessica S. Donington
7Department of Surgery, University of Chicago, Chicago, IL 60637, USA
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Florian Krammer
8Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Daved H. Fremont
5Department of Pathology and Immunology and Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, Washington University School of Medicine, St. Louis, MO 63110, USA
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Andrzej Joachimiak
9Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL 60667
10Structural Biology Center, X-ray Science Division, Argonne National Laboratory, Argonne, IL 60439, USA
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Yoshihiro Kawaoka
2Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53711
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Vera Tesic
11Department of Pathology, University of Chicago, Chicago, IL 60637, USA
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Maria Lucia Madariaga
7Department of Surgery, University of Chicago, Chicago, IL 60637, USA
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Patrick C. Wilson
1Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
3Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
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  • For correspondence: jguthmiller@uchicago.edu wilsonp@uchicago.edu
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ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity and kinetics of the antibody response mounted against this novel virus are not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and non-structural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted September 13, 2020.
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SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike
Jenna J. Guthmiller, Olivia Stovicek, Jiaolong Wang, Siriruk Changrob, Lei Li, Peter Halfmann, Nai-Ying Zheng, Henry Utset, Christopher T. Stamper, Haley L. Dugan, William D. Miller, Min Huang, Ya-Nan Dai, Christopher A. Nelson, Paige D. Hall, Maud Jansen, Kumaran Shanmugarajah, Jessica S. Donington, Florian Krammer, Daved H. Fremont, Andrzej Joachimiak, Yoshihiro Kawaoka, Vera Tesic, Maria Lucia Madariaga, Patrick C. Wilson
bioRxiv 2020.09.12.294066; doi: https://doi.org/10.1101/2020.09.12.294066
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SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike
Jenna J. Guthmiller, Olivia Stovicek, Jiaolong Wang, Siriruk Changrob, Lei Li, Peter Halfmann, Nai-Ying Zheng, Henry Utset, Christopher T. Stamper, Haley L. Dugan, William D. Miller, Min Huang, Ya-Nan Dai, Christopher A. Nelson, Paige D. Hall, Maud Jansen, Kumaran Shanmugarajah, Jessica S. Donington, Florian Krammer, Daved H. Fremont, Andrzej Joachimiak, Yoshihiro Kawaoka, Vera Tesic, Maria Lucia Madariaga, Patrick C. Wilson
bioRxiv 2020.09.12.294066; doi: https://doi.org/10.1101/2020.09.12.294066

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