Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant

  1. Dong-Kyun Ryu
  2. Rina Song
  3. Minsoo Kim
  4. Young-Il Kim
  5. Cheolmin Kim
  6. Jong-In Kim
  7. Ki-Sung Kwon
  8. Aloys SL Tijsma
  9. Patricia M Nuijten
  10. Carel A van Baalen
  11. Tandile Hermanus
  12. Prudence Kgagudi
  13. Thandeka Gwete-Moyo
  14. Penny L Moore
  15. Young Ki Choi
  16. Soo-Young Lee

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Abstract

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.

Highlights

  • CT-P59 significantly inhibit B.1.1.7 variant to a similar extent as to wild type virus

  • CT-P59 showed reduced potency against the B.1.351 variant in in vitro studies

  • Therapeutic dosage of CT-P59 showed in vivo neutralizing potency against B.1.351 in ferret challenge study.

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  1. ScreenIT

    SciScore for 10.1101/2021.04.27.441707: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: For in vivo study, NMC-nCoV02 (S clade) and hCoV-19/Korea/KDCA55905/202 (B.1.351) were provided by National Culture Collection for Pathogens. 2.2.
    IACUC: All animal cares were performed strictly following the animal care guideline and experiment protocols approved by Institutional Animal Care and Use Committee (IACUC) in Chungbuk National University (
    Sex as a biological variableFerret study: Groups of 14- to 16-month-old female ferrets (
    Randomizationnot detected.
    BlindingCough, rhinorrhea and movement were scored and analyzed for each animal in blind manner. 2.8.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Following blocking, serially diluted CT-P59 were incubated, followed by an anti-human horseradish peroxidase-conjugated antibody.
    anti-human horseradish peroxidase-conjugated antibody .
    suggested: None
    The cells were formalin-fixed and ethanol permeabilized followed by incubation with a murine monoclonal antibody which targets the viral nucleocapsid protein (Sino Biological), followed by a secondary anti-mouse IgG peroxidase conjugate (Thermo Scientific) and TrueBlue (KPL) substrate.
    anti-mouse IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cells and viruses: VeroE6 cells (ATCC, CRL-1586) were cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% (v/v
    VeroE6
    suggested: None
    Software and Algorithms
    SentencesResources
    Images of all wells were acquired by a CTL Immunospot analyzer, equipped with Biospot® software to quantitate the nucleocapsid-positive cells (= virus signal).
    Biospot®
    suggested: None
    Virus titer and viral RNA from animals were analyzed using GraphPad Prism v 9.1.0.
    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: 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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.04.27.441707 on bioRxiv