Pathogenicity, immunogenicity, and protective ability of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein

  1. Pui Wang
  2. Siu-Ying Lau
  3. Shaofeng Deng
  4. Pin Chen
  5. Bobo Wing-Yee Mok
  6. Anna Jinxia Zhang
  7. Andrew Chak-Yiu Lee
  8. Kwok-Hung Chan
  9. Wenjun Song
  10. Kelvin Kai-Wang To
  11. Jasper Fuk-Woo Chan
  12. Kwok-Yung Yuen
  13. Honglin Chen

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Abstract

SARS-CoV-2 contains a PRRA polybasic cleavage motif considered critical for efficient infection and transmission in humans. We previously reported that virus variants with spike protein S1/S2 junction deletions spanning this motif are attenuated. Here we characterize a further cell-adapted SARS-CoV-2 variant, Ca-DelMut. Ca-DelMut replicates more efficiently than wild type or parental virus in cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut does not induce proinflammatory cytokines in hamster infections, but still triggers a strong neutralizing antibody response. Ca-DelMut-immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, demonstrating sterilizing immunity.

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    SciScore for 10.1101/2020.08.24.264192: (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
    At day 21, sera were collected from hamsters for anti-spike RBD IgG and neutralizing antibody determination.
    anti-spike RBD IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Growth kinetics: Confluent Vero E6 or Calu-3 cells were infected at 0.01 moi with the indicated viruses and incubated for 3 days.
    Calu-3
    suggested: KCLB Cat# 30055, RRID:CVCL_0609)
    Plaque assay: Confluent Vero E6 cells in 6-well format were incubated with 10-fold serially diluted virus for 1 h.
    Vero E6
    suggested: None

    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.
    • 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

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  2. Version published to 10.1101/2020.08.24.264192v1 on bioRxiv