Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

  1. Philip J. M. Brouwer
  2. Tom G. Caniels
  3. Karlijn van der Straten
  4. Jonne L. Snitselaar
  5. Yoann Aldon
  6. Sandhya Bangaru
  7. Jonathan L. Torres
  8. Nisreen M. A. Okba
  9. Mathieu Claireaux
  10. Gius Kerster
  11. Arthur E. H. Bentlage
  12. Marlies M. van Haaren
  13. Denise Guerra
  14. Judith A. Burger
  15. Edith E. Schermer
  16. Kirsten D. Verheul
  17. Niels van der Velde
  18. Alex van der Kooi
  19. Jelle van Schooten
  20. Mariëlle J. van Breemen
  21. Tom P. L. Bijl
  22. Kwinten Sliepen
  23. Aafke Aartse
  24. Ronald Derking
  25. Ilja Bontjer
  26. Neeltje A. Kootstra
  27. W. Joost Wiersinga
  28. Gestur Vidarsson
  29. Bart L. Haagmans
  30. Andrew B. Ward
  31. Godelieve J. de Bree
  32. Rogier W. Sanders
  33. Marit J. van Gils

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Abstract

Antibodies that neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be an important tool in treating coronavirus disease 2019 (COVID-19). Brouwer et al. isolated 403 monoclonal antibodies from three convalescent COVID-19 patients. They show that the patients had strong immune responses against the viral spike protein, a complex that binds to receptors on the host cell. A subset of antibodies was able to neutralize the virus. Competition and electron microscopy studies showed that these antibodies target diverse epitopes on the spike, with the two most potent targeting the domain that binds the host receptor.

Science , this issue p. 643

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  1. Version published to 10.1126/science.abc5902
  2. ScreenIT

    SciScore for 10.1101/2020.05.12.088716: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.RandomizationSafety and efficacy of monoclonal antibody VIS410 in adults with uncomplicated influenza A infection: Results from a randomized, double-blind, phase-2, placebo-controlled study.Blindingnot detected.Power Analysisnot detected.Sex as a biological variableCOSCA1 (47-yearold male) and COSCA2 (44-year-old female) showed symptoms of an upper respiratory tract infection and mild pneumonia, respectively (Table 1).Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Several of these antibodies were able to potently inhibit live SARS-CoV-2 infection at concentrations as low as 0.007 µg/mL, making them the most potent human SARS-CoV-2 antibodies described to date.
    SARS-CoV-2
    suggested: None
    Indeed, therapeutic antibody cocktails with a variety of specificities have been used successfully against Ebola virus disease (7) and are being tested widely in clinical trials for HIV-1 (28).
    HIV-1 (28
    suggested: None
    A hallmark of antibody diversity is the heavy chain complementarity determining region 3 (CDRH3).
    CDRH3
    suggested: None
    The average length of CDRH3 in the naive human repertoire is 15 amino acids (34), but for a subset of influenza virus and HIV-1 broadly neutralizing antibodies, long CDRH3 regions of 20-35 amino acids are crucial for high affinity antigen-antibody interactions (35, 36).
    HIV-1 broadly neutralizing antibodies, long CDRH3
    suggested: None
    With IC50s of 0.008 µg/mL the RBD-targeting antibodies COVA1-18 and COVA2-15, in particular, were remarkably potent while being quite different in other aspects such as their heavy chain V gene usage (VH3-66 vs. VH3-23), light chain usage (VL7-46 vs. VK2-30), HC sequence identity (77%) and CDRH3 length (12 vs. 22 amino acids).
    COVA2-15
    suggested: None
    In conclusion, convalescent COVID-19 patients showed strong anti-SARS-CoV-2 S protein specific B cell responses and developed memory and antibody producing B cells that may have participated in the control of infection and the establishment of humoral immunity.
    anti-SARS-CoV-2 S
    suggested: None
    Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor.
    angiotensin converting enzyme 2 receptor.
    suggested: None
    Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution.
    human neutralizing antibodies against MERS-CoV
    suggested: None
    Nat Commun 8, 15371 (2017). L. Yu, Y. Guan, Immunologic Basis for Long HCDR3s in Broadly Neutralizing Antibodies Against HIV-1. Front Immunol 5, 250 (2014). F. Chen, N. Tzarum, I. A. Wilson, M. Law, VH1-69 antiviral broadly neutralizing antibodies: genetics, structures, and relevance to rational vaccine design.
    VH1-69
    suggested: None
    An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability.
    HIV-1
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Subsequently, all HC and LC pairs were transiently expressed in HEK 293T cells and screened for binding by ELISA to SARS-CoV-2 S protein.
    HEK 293T
    suggested: KCB Cat# KCB 200744YJ, CVCL_0063
    84 mAbs that showed potent binding were selected for small-scale expression in HEK 293F cells and purified.
    HEK 293F
    suggested: CVCL_6642
    Software and Algorithms
    SentencesResources
    Structural and functional analysis of a potent sarbecovirus neutralizing antibody. bioRxiv, 2020.2004.2007.023903 (2020). X. Chen et al.,
    bioRxiv
    suggested: (bioRxiv, SCR_003933)
    N. R. Voss, C. K. Yoshioka, M. Radermacher, C. S. Potter, B. Carragher, DoG Picker and TiltPicker: software tools to facilitate particle selection in single particle electron microscopy.
    TiltPicker
    suggested: (TiltPicker, SCR_016674)

    We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).

    About SciScore

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  3. Version published to 10.1101/2020.05.12.088716v1 on bioRxiv