Establishment of an African green monkey model for COVID-19

  1. Courtney Woolsey
  2. Viktoriya Borisevich
  3. Abhishek N. Prasad
  4. Krystle N. Agans
  5. Daniel J. Deer
  6. Natalie S. Dobias
  7. John C. Heymann
  8. Stephanie L. Foster
  9. Corri B. Levine
  10. Liana Medina
  11. Kevin Melody
  12. Joan B. Geisbert
  13. Karla A. Fenton
  14. Thomas W. Geisbert
  15. Robert W. Cross

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen candidate vaccines and treatments. Nonhuman primates (NHP) are considered the gold standard model for many infectious pathogens as they usually best reflect the human condition. Here, we show that African green monkeys support a high level of SARS-CoV-2 replication and develop pronounced respiratory disease that may be more substantial than reported for other NHP species including cynomolgus and rhesus macaques. In addition, SARS-CoV-2 was detected in mucosal samples of all animals including feces of several animals as late as 15 days after virus exposure. Importantly, we show that virus replication and respiratory disease can be produced in African green monkeys using a much lower and more natural dose of SARS-CoV-2 than has been employed in other NHP studies.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.17.100289: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: All animal studies were approved by the University of Texas Medical Branch (UTMB) Institutional Animal Care and Use Committee and adhere to the NIH Guide for the Care and Use of Laboratory Animals.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    ELISA: Sera collected at the indicated time points were tested for SARS-CoV-2-specific immunoglobulin G (IgG) antibodies by ELISA.
    SARS-CoV-2-specific immunoglobulin G ( IgG
    suggested: None
    After a one-hour incubation, plates were washed six times with wash buffer (1 x PBS with 0.2% Tween-20) and incubated for an hour with a 1:2500 dilution of horseradish peroxidase (HRP)-conjugated anti-primate IgG antibody (Fitzgerald Industries International, Acton, MA).
    anti-primate IgG
    suggested: None
    For IHC, specific anti-SARS immunoreactivity was detected using an anti-SARS nucleocapsid protein rabbit primary antibody at a 1:800 dilution for 60 minutes (Novusbio NB100-56683).
    anti-SARS
    suggested: None
    anti-SARS nucleocapsid protein
    suggested: None
    Secondary antibody used was biotinylated goat anti-rabbit IgG (Vector Laboratories, Burlingame, CA) at 1:200 for 30 minutes followed by Vector Streptavidin Alkaline Phosphatase at a dilution of 1:200 for 20 min (Vector Laboratories, Burlingame, CA).
    anti-rabbit IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The virus was initially passaged twice (P2) on Vero E6 cells; the supernatant and cell lysate were collected and clarified following a freeze/thaw cycle.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Partial pressures of CO2 and O2 were obtained using an iSTAT Alinity hematological analyzer (Abbott).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)

    Results from OddPub: Thank you for sharing your data.

    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.

  2. Version published to 10.1101/2020.05.17.100289v1 on bioRxiv