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

  1. Priyamvada Acharya
  2. Wilton Williams
  3. Rory Henderson
  4. Katarzyna Janowska
  5. Kartik Manne
  6. Robert Parks
  7. Margaret Deyton
  8. Jordan Sprenz
  9. Victoria Stalls
  10. Megan Kopp
  11. Katayoun Mansouri
  12. Robert J Edwards
  13. R. Ryan Meyerhoff
  14. Thomas Oguin
  15. Gregory Sempowski
  16. Kevin Saunders
  17. Barton F. Haynes

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Abstract

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.

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  1. ScreenIT

    SciScore for 10.1101/2020.06.30.178897: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody 2G12 was obtained from three sources, either produced from two sources as described from the original sequence (17) 2G12_G1M17 or 2G12-rV2, or purchased from Polymun, Vienna Austria.
    2G12-rV2
    suggested: None
    Mouse anti-monkey IgG-HRP (Southern Biotech, CAT# 4700-05) or Goat anti-human IgG-HRP (Jackson ImmunoResearch Laboratories, CAT# 109-035-098) secondary antibodies were used to detect mAb bound to the SARS-CoV-2 spike protein.
    anti-monkey IgG-HRP
    suggested: (SouthernBiotech Cat# 4700-05, RRID:AB_2796069)
    anti-human IgG-HRP
    suggested: None
    SARS-CoV-2 spike protein.
    suggested: None
    Software and Algorithms
    SentencesResources
    The RELION program was used to perform class averaging of the single-particle images.
    RELION
    suggested: (RELION, RRID:SCR_016274)
    Coordinates were then fit manually in Coot (23) following iterative refinement using Isolde (22) and subsequent manual coordinate fitting in Coot.
    Coot
    suggested: (Coot, RRID:SCR_014222)
    Structure and map analysis was performed using PyMol and ChimeraX (41).
    PyMol
    suggested: (PyMOL, RRID:SCR_000305)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 42 and 23. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.06.30.178897v1 on bioRxiv