A panel of human neutralizing mAbs targeting SARS-CoV-2 spike at multiple epitopes

  1. Tal Noy-Porat
  2. Efi Makdasi
  3. Ron Alcalay
  4. Adva Mechaly
  5. Yinon Levy
  6. Adi Bercovich-Kinori
  7. Ayelet Zauberman
  8. Hadas Tamir
  9. Yfat Yahalom-Ronen
  10. Ma’ayan Israeli
  11. Eyal Epstein
  12. Hagit Achdout
  13. Sharon Melamed
  14. Theodor Chitlaru
  15. Shay Weiss
  16. Eldar Peretz
  17. Osnat Rosen
  18. Nir Paran
  19. Shmuel Yitzhaki
  20. Shmuel C. Shapira
  21. Tomer Israely
  22. Ohad Mazor
  23. Ronit Rosenfeld

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Abstract

The novel highly transmissible human coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Thus far, there is no approved therapeutic drug specifically targeting this emerging virus. Here we report the isolation and characterization of a panel of human neutralizing monoclonal antibodies targeting the SARS-CoV-2 receptor binding domain (RBD). These antibodies were selected from a phage display library constructed using peripheral circulatory lymphocytes collected from patients at the acute phase of the disease. These neutralizing antibodies are shown to recognize distinct epitopes on the viral spike RBD. A subset of the antibodies exert their inhibitory activity by abrogating binding of the RBD to the human ACE2 receptor. The human monoclonal antibodies described here represent a promising basis for the design of efficient combined post-exposure therapy for SARS-CoV-2 infection.

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  1. Version published to 10.1038/s41467-020-18159-4
  2. Version published to 10.1101/2020.05.20.106609v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.05.20.106609: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Blood samples: Sera and whole blood samples collected from five convalescent or severe COVID-19 patients were obtained under written inform consent and treated in accordance with the biosafety guidelines of the IIBR in BL3 facility.
    IACUC: The study was approved by the Sheba Medical Center IRB Ethical Committee as well as by the Baruch Padeh Medical Center IRB Ethical Committee.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Production of scFv-Fc Antibodies: Phagemid DNA of the desired clones were isolated using QIAprep spin Miniprep kit (Qiagen, GmbH, Hilden, Germany), and the entire scFv was cloned into a pcDNA3.1+ based expression vector that was modified, providing the scFv with the human (IgG1) CH2-CH3 Fc fragments, resulting in scFv-Fc antibody format.
    IgG1
    suggested: None
    For phage ELISA, HRP-conjugated anti-M13 antibody (Sino Biologicals, USA) was used following detection with TMB substrate (Millipore, USA).
    anti-M13
    suggested: None
    ELISA of both sera and recombinant scFv-Fc human antibodies applied with AP-conjugated anti-human IgG (Jackson ImmunoResearch, USA) following detection using PNPP substrate (Sigma, Israel).
    anti-human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Stocks were prepared by infection of Vero E6 cells for two days.
    Vero E6
    suggested: RRID:CVCL_XD71)

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  4. Version published to 10.1101/2020.05.20.106609v1 on bioRxiv