Post-exposure protection of SARS-CoV-2 lethal infected K18-hACE2 transgenic mice by neutralizing human monoclonal antibody

  1. Ronit Rosenfeld
  2. Tal Noy-Porat
  3. Adva Mechaly
  4. Efi Makdasi
  5. Yinon Levy
  6. Ron Alcalay
  7. Reut Falach
  8. Moshe Aftalion
  9. Eyal Epstein
  10. David Gur
  11. Theodor Chitlaru
  12. Einat B. Vitner
  13. Sharon Melamed
  14. Boaz Politi
  15. Ayelet Zauberman
  16. Shirley Lazar
  17. Adi Beth-Din
  18. Yentl Evgy
  19. Shmuel Yitzhaki
  20. Shmuel C. Shapira
  21. Tomer Israely
  22. Ohad Mazor

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Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits high levels of mortality and morbidity and has dramatic consequences on human life, sociality and global economy. Neutralizing antibodies constitute a highly promising approach for treating and preventing infection by this novel pathogen. In the present study, we characterize and further evaluate the recently identified human monoclonal MD65 antibody for its ability to provide protection against a lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice. Eighty percent of the untreated mice succumbed 6–9 days post-infection, while administration of the MD65 antibody as late as 3 days after exposure rescued all infected animals. In addition, the efficiency of the treatment is supported by prevention of morbidity and ablation of the load of infective virions in the lungs of treated animals. The data demonstrate the therapeutic value of human monoclonal antibodies as a life-saving treatment for severe COVID-19 infection.

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  1. Version published to 10.1038/s41467-021-21239-8
  2. Version published to 10.1101/2020.10.26.354811v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.10.26.354811: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Animal experiments: Treatment of animals was in accordance with regulations outlined in the U.S. Department of Agriculture (USDA) Animal Welfare Act and the conditions specified in the Guide for Care and Use of Laboratory Animals (National Institute of Health, 2011).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableMale and female K18-hACE2 transgenic (B6.Cg-Tg(K18-ACE2)2Prlmn/J HEMI) and C57BL/6 mice (Jackson Laboratories, USA) were maintained at 20−22 °C and a relative humidity of 50 ± 10% on a 12 h light/dark cycle, fed with commercial rodent chow (Koffolk Inc.) and provided with tap water ad libitum.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Recombinant antibodies (scFv-Fc, IgG and IgG-YTE) were expressed using ExpiCHO™ Expression system (Thermoscientific, USA, Cat# A29133) and purified on HiTrap Protein-A column (GE healthcare, UK).
    scFv-Fc, IgG
    suggested: None
    IgG-YTE
    suggested: None
    Measurement of viral RNA by qRT-PCR: Viral load in lungs of SARS-CoV-2 infected mice (200 PFU) treated with the MD65 antibody, was quantified by qRT-PCR and by plaque assay (see above).
    MD65
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus stocks were propagated and tittered by infection of Vero E6 cells as recently described44.
    Vero E6
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Male and female K18-hACE2 transgenic (B6.Cg-Tg(K18-ACE2)2Prlmn/J HEMI) and C57BL/6 mice (Jackson Laboratories, USA) were maintained at 20−22 °C and a relative humidity of 50 ± 10% on a 12 h light/dark cycle, fed with commercial rodent chow (Koffolk Inc.) and provided with tap water ad libitum.
    B6.Cg-Tg(K18-ACE2)2Prlmn/J HEMI
    suggested: None
    C57BL/6
    suggested: None
    Software and Algorithms
    SentencesResources
    The number of plaques in each well was scored and the NT50 (Ab concentration at which the plaque number was reduced by 50%, compared to plaque number of the control, in the absence of Ab), was calculated using the Prism software version 8 (GraphPad Software Inc., USA).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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 10.1101/2020.10.26.354811v1 on bioRxiv