SARS-CoV-2 Neutralizing Human Antibodies Protect Against Lower Respiratory Tract Disease in a Hamster Model

  1. Bart L Haagmans
  2. Danny Noack
  3. Nisreen M A Okba
  4. Wentao Li
  5. Chunyan Wang
  6. Theo Bestebroer
  7. Rory de Vries
  8. Sander Herfst
  9. Dennis de Meulder
  10. Elwin Verveer
  11. Peter van Run
  12. Mart M Lamers
  13. Bart Rijnders
  14. Casper Rokx
  15. Frank van Kuppeveld
  16. Frank Grosveld
  17. Dubravka Drabek
  18. Corine Geurts van Kessel
  19. Marion Koopmans
  20. Berend Jan Bosch
  21. Thijs Kuiken
  22. Barry Rockx

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Abstract

Effective clinical intervention strategies for coronavirus disease 2019 (COVID-19) are urgently needed. Although several clinical trials have evaluated use of convalescent plasma containing virus-neutralizing antibodies, levels of neutralizing antibodies are usually not assessed and the effectiveness has not been proven. We show that hamsters treated prophylactically with a 1:2560 titer of human convalescent plasma or a 1:5260 titer of monoclonal antibody were protected against weight loss, had a significant reduction of virus replication in the lungs, and showed reduced pneumonia. Interestingly, this protective effect was lost with a titer of 1:320 of convalescent plasma. These data highlight the importance of screening plasma donors for high levels of neutralizing antibodies. Our data show that prophylactic administration of high levels of neutralizing antibody, either monoclonal or from convalescent plasma, prevent severe SARS-CoV-2 pneumonia in a hamster model, and could be used as an alternative or complementary to other antiviral treatments for COVID-19.

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  1. Version published to 10.1093/infdis/jiab289
  2. ScreenIT

    SciScore for 10.1101/2020.08.24.264630: (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.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serological Analysis: To test for SARS-CoV-2 antibodies, hamster serum samples were collected at days 4 and 22
    SARS-CoV-2
    suggested: None
    Bound antibodies were detected using HRP-labelled rabbit anti–human IgG (Dako) or anti-hamster IgG and TMB (Life Technologies) as a substrate.
    anti–human IgG
    suggested: None
    anti-hamster IgG
    suggested: None
    Briefly, paraffin was removed from sections, and viral antigen was detected using a rabbit polyclonal antibody against SARS-CoV-nucleoprotein (40143-T62, Sino Biological, Chesterbrook, PA, USA) and horseradish peroxidase labeled goat-anti-rabbit IgG (P0448, DAKO, Agilent Technologies Netherlands B.V. Amstelveen, The Netherlands).
    antibody against SARS-CoV-nucleoprotein
    suggested: None
    IgG (P0448
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The virus was propagated to passage three on Vero E6 cells in Opti-MEM I (1X) + GlutaMAX (Gibco), supplemented with penicillin (10,000 IU/mL) and streptomycin (10,000 IU/mL) at 37°C in a humidified CO2 incubator.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Statistical analyses were performed using GraphPad Prism 5 software (La Jolla, CA, USA).
    GraphPad Prism
    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: We detected the following sentences addressing limitations in the study:
    No such limitation is present with in vitro produced MAbs and our results suggest this may be the more favorable route to develop an effective therapy.

    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. Version published to 10.1101/2020.08.24.264630v1 on bioRxiv