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A glycan cluster on the SARS-CoV-2 spike ectodomain is recognized by Fab-dimerized glycan-reactive antibodies

View ORCID ProfilePriyamvada Acharya, Wilton Williams, Rory Henderson, Katarzyna Janowska, Kartik Manne, Robert Parks, Margaret Deyton, Jordan Sprenz, Victoria Stalls, Megan Kopp, Katayoun Mansouri, Robert J Edwards, R. Ryan Meyerhoff, Thomas Oguin, Gregory Sempowski, Kevin Saunders, Barton F. Haynes
doi: https://doi.org/10.1101/2020.06.30.178897
Priyamvada Acharya
1Duke Human Vaccine Institute, Durham NC 27710, USA
2Duke University, Department of Surgery, Durham NC 27710, USA
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  • ORCID record for Priyamvada Acharya
  • For correspondence: priyamvada.acharya@duke.edu hayne002@mc.duke.edu
Wilton Williams
1Duke Human Vaccine Institute, Durham NC 27710, USA
3Duke University, Department of Medicine, Durham NC 27710, USA
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Rory Henderson
1Duke Human Vaccine Institute, Durham NC 27710, USA
3Duke University, Department of Medicine, Durham NC 27710, USA
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Katarzyna Janowska
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Kartik Manne
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Robert Parks
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Margaret Deyton
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Jordan Sprenz
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Victoria Stalls
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Megan Kopp
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Katayoun Mansouri
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Robert J Edwards
1Duke Human Vaccine Institute, Durham NC 27710, USA
3Duke University, Department of Medicine, Durham NC 27710, USA
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R. Ryan Meyerhoff
1Duke Human Vaccine Institute, Durham NC 27710, USA
3Duke University, Department of Medicine, Durham NC 27710, USA
5Duke University, Division of Interventional Radiology, Department of Radiology, Durham NC 27710, USA
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Thomas Oguin
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Gregory Sempowski
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Kevin Saunders
1Duke Human Vaccine Institute, Durham NC 27710, USA
2Duke University, Department of Surgery, Durham NC 27710, USA
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Barton F. Haynes
1Duke Human Vaccine Institute, Durham NC 27710, USA
3Duke University, Department of Medicine, Durham NC 27710, USA
4Duke University, Department of Immunology, Durham NC 27710, USA
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  • For correspondence: priyamvada.acharya@duke.edu hayne002@mc.duke.edu
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Summary

The COVID-19 pandemic caused by SARS-CoV-2 has escalated into a global crisis. The spike (S) protein that mediates cell entry and membrane fusion is the current focus of vaccine and therapeutic antibody development efforts. The S protein, like many other viral fusion proteins such as HIV-1 envelope (Env) and influenza hemagglutinin, is glycosylated with both complex and high mannose glycans. Here we demonstrate binding to the SARS-CoV-2 S protein by a category of Fab-dimerized glycan-reactive (FDG) HIV-1-induced broadly neutralizing antibodies (bnAbs). A 3.1 Å resolution cryo-EM structure of the S protein ectodomain bound to glycan-dependent HIV-1 bnAb 2G12 revealed a quaternary glycan epitope on the spike S2 domain involving multiple protomers. These data reveal a new epitope on the SARS-CoV-2 spike that can be targeted for vaccine design.

Highlights

  • Fab-dimerized, glycan-reactive (FDG) HIV-1 bnAbs cross-react with SARS-CoV-2 spike.

  • 3.1 Å resolution cryo-EM structure reveals quaternary S2 epitope for HIV-1 bnAb 2G12.

  • 2G12 targets glycans, at positions 709, 717 and 801, in the SARS-CoV-2 spike.

  • Our studies suggest a common epitope for FDG antibodies centered around glycan 709.

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. All rights reserved. No reuse allowed without permission.
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Posted June 30, 2020.
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A glycan cluster on the SARS-CoV-2 spike ectodomain is recognized by Fab-dimerized glycan-reactive antibodies
Priyamvada Acharya, Wilton Williams, Rory Henderson, Katarzyna Janowska, Kartik Manne, Robert Parks, Margaret Deyton, Jordan Sprenz, Victoria Stalls, Megan Kopp, Katayoun Mansouri, Robert J Edwards, R. Ryan Meyerhoff, Thomas Oguin, Gregory Sempowski, Kevin Saunders, Barton F. Haynes
bioRxiv 2020.06.30.178897; doi: https://doi.org/10.1101/2020.06.30.178897
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A glycan cluster on the SARS-CoV-2 spike ectodomain is recognized by Fab-dimerized glycan-reactive antibodies
Priyamvada Acharya, Wilton Williams, Rory Henderson, Katarzyna Janowska, Kartik Manne, Robert Parks, Margaret Deyton, Jordan Sprenz, Victoria Stalls, Megan Kopp, Katayoun Mansouri, Robert J Edwards, R. Ryan Meyerhoff, Thomas Oguin, Gregory Sempowski, Kevin Saunders, Barton F. Haynes
bioRxiv 2020.06.30.178897; doi: https://doi.org/10.1101/2020.06.30.178897

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