A glycan cluster on the SARS-CoV-2 spike ectodomain is recognized by Fab-dimerized glycan-reactive antibodies
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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
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Fab-dimerized, glycan-reactive (FDG) HIV-1 bnAbs cross-react with SARS-CoV-2 spike.
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3.1 Å resolution cryo-EM structure reveals quaternary S2 epitope for HIV-1 bnAb 2G12.
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2G12 targets glycans, at positions 709, 717 and 801, in the SARS-CoV-2 spike.
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Our studies suggest a common epitope for FDG antibodies centered around glycan 709.
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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 Sentences Resources 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-rV2suggested: NoneMouse 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-HRPsuggested: (SouthernBiotech Cat# 4700-05, RRID:AB_2796069)anti-human IgG-HRPsuggested: NoneSARS-CoV-2 spike protein.suggested: None… 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 Sentences Resources 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-rV2suggested: NoneMouse 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-HRPsuggested: (SouthernBiotech Cat# 4700-05, RRID:AB_2796069)anti-human IgG-HRPsuggested: NoneSARS-CoV-2 spike protein.suggested: NoneSoftware and Algorithms Sentences Resources The RELION program was used to perform class averaging of the single-particle images. RELIONsuggested: (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. Cootsuggested: (Coot, RRID:SCR_014222)Structure and map analysis was performed using PyMol and ChimeraX (41). PyMolsuggested: (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.
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