An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain

  1. Nicholas C. Wu
  2. Meng Yuan
  3. Hejun Liu
  4. Chang-Chun D. Lee
  5. Xueyong Zhu
  6. Sandhya Bangaru
  7. Jonathan L. Torres
  8. Tom G. Caniels
  9. Philip J.M. Brouwer
  10. Marit J. van Gils
  11. Rogier W. Sanders
  12. Andrew B. Ward
  13. Ian A. Wilson

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Abstract

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  1. Version published to 10.1016/j.celrep.2020.108274
  2. ScreenIT

    SciScore for 10.1101/2020.07.26.222232: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Biolayer interferometry binding assay: Antibody binding and competition assays were performed by biolayer interferometry (BLI) using an Octet Red instrument (FortéBio) as described previously (Wu et al., 2017), with anti-human Fab-CH1 2nd generation (FAB2G) biosensors.
    anti-human Fab-CH1
    suggested: None
    Software and Algorithms
    SentencesResources
    Iterative model building and refinement were carried out in COOT (Emsley et al., 2010) and PHENIX (Adams et al., 2010), respectively.
    COOT
    suggested: (Coot, RRID:SCR_014222)
    PHENIX
    suggested: (Phenix, RRID:SCR_014224)

    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: We did not find any issues relating to colormaps.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. ScreenIT

    SciScore for 10.1101/2020.07.26.222232: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Biolayer interferometry binding assay Antibody binding and competition assays were performed by biolayer interferometry (BLI) using an Octet Red instrument (FortéBio) as described previously (Wu et al., 2017), with anti-human Fab-CH1 2nd generation (FAB2G) biosensors.
    anti-human Fab-CH1
    suggested: None
    Software and Algorithms
    SentencesResources
    Iterative model building and refinement were carried out in COOT (Emsley et al., 2010) and PHENIX (Adams et al., 2010), respectively.
    COOT
    suggested: (Coot, RRID:SCR_014222)
    PHENIX
    suggested: (Phenix, RRID:SCR_014224)

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

    Results from JetFighter: We did not find any issues relating to colormaps.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. ScreenIT

    SciScore for 10.1101/2020.07.26.222232: (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
    Overall, these findings emphasize the versatility of IGHV3-53 in this common antibody response to SARS-CoV-2, where conserved IGHV3-53 germline-encoded features can be combined with very different CDR H3 lengths and light chains for SARS-CoV-2 RBD recognition and virus neutralization.
    SARS-CoV-2
    suggested: None
    RESULTS Two RBD-targeting IGHV3-53 antibodies with different binding modes We determined crystal structures of two IGHV3-53 neutralizing antibodies, COVA2-04 and COVA2-39 (Brouwer et al., 2020), with different CDR H3 lengths in complex with SARSCoV-2 RBD to 2.35 and 1.72 Å resolutions, respectively (Figure 1A and Table S1).
    IGHV3-53
    suggested: None
    The binding mode of COVA2-04 is very similar to previously characterized IGHV3-53 antibodies with a short CDR H3, including CC12.1, CC12.3, B38, and C105 (Barnes et al., 2020; Wu et al., 2020; Yuan et al., 2020a
    C105
    suggested: (Leinco Technologies Cat# C105, AB_2828317)
    The CDR H3 sequences of IGHV3-53 antibodies in binding mode A (COVA2-04, CC12.1, CC12.3, and B38) are also quite different (Wu et al., 2020; Yuan et al., 2020a) (Figure 4D).
    B38
    suggested: None
    Nonetheless, additional structures of RBD-targeting IGHV353 antibodies with longer CDR H3s should further aid in explaining the differential occurrence frequency between binding modes A and B.
    IGHV353
    suggested: None
    (A, C) Interactions are shown between RBD (white) and signature 32NY33 motifs on the CDR H1 loop of VH3-53 antibodies (A) COVA2-04 (cyan), and (C) COVA2-39. (B, D) RBD forms an extensive hydrogen bonding network with (B) COVA2-04, and (D) 53TGGT56 53SGGS56 motif on the CDR H2 loop of motif on the CDR H2 loop of COVA2-39.
    VH3-53
    suggested: None
          <div style="margin-bottom:8px">
        <div><b>COVA2-04</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>COVA2-39</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Biolayer interferometry binding assay Antibody binding and competition assays were performed by biolayer interferometry (BLI) using an Octet Red instrument (FortéBio) as described previously (Wu et al., 2017), with anti-human Fab-CH1 2nd generation (FAB2G) biosensors.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>anti-human Fab-CH1</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Software and Algorithms</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Iterative model building and refinement were carried out in COOT (Emsley et al., 2010) and PHENIX (Adams et al., 2010), respectively.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>COOT</b></div>
        <div>suggested: (Coot, <a href="https://scicrunch.org/resources/Any/search?q=SCR_014222">SCR_014222</a>)</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>PHENIX</b></div>
        <div>suggested: (Phenix, <a href="https://scicrunch.org/resources/Any/search?q=SCR_014224">SCR_014224</a>)</div>
      </div>
    </td></tr></table>

    Data from additional tools added to each annotation on a weekly basis.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  5. Version published to 10.1101/2020.07.26.222232v1 on bioRxiv