The in vitro and in vivo potency of CT-P59 against Delta and its associated variants of SARS-CoV-2

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Abstract

The Delta variant originally from India is rapidly spreading across the world and causes to resurge infections of SARS-CoV-2. We previously reported that CT-P59 presented its in vivo potency against Beta and Gamma variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on the Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal study. CT-P59 showed reduced antiviral activity but enabled neutralization against Delta, Epsilon, and Kappa variants in cells. In line with in vitro results, the mouse challenge experiment with the Delta variant substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against the Delta variant infection, hinting that CT-P59 has therapeutic potency for patients infected with Delta and its associated variants.

Highlights

  • CT-P59 exerts the antiviral effect on authentic Delta, Epsilon and Kappa variants in cell-based experiments.

  • CT-P59 showed neutralizing potency against variants including Delta, Epsilon, Kappa, L452R, T478K and P681H pseudovirus variants.

  • The administration of clinically relevant dose of CT-P59 showed in vivo

  • protection against Delta variants in animal challenge experiment.

Article activity feed

  1. SciScore for 10.1101/2021.07.23.453472: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: All procedures were approved by the Institutional Animal Care and Use Committee at KDCA (No. KDCA-IACUC-21-026). 2.6.
    Sex as a biological variableAnimal experiments: 8-week-old female human ACE2 transgenic mice, tg(K18-ACE2)2Prlmn, were purchased from The Jackson Laboratory.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Briefly, pre-incubated mixture of variant and CT-P59 was inoculated to VeroE6 cells.
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    The mixture inoculated ACE2-HEK293T cells, and incubated for 72 h.
    ACE2-HEK293T
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Animal experiments: 8-week-old female human ACE2 transgenic mice, tg(K18-ACE2)2Prlmn, were purchased from The Jackson Laboratory.
    tg(K18-ACE2)2Prlmn
    suggested: RRID:IMSR_JAX:035247)
    Software and Algorithms
    SentencesResources
    After incubation, the neutralization of CT-P59 against each variant was determined as the half-maximal inhibitory concentration (IC50) using GraphPad Prism6 software. 2.4. Pseudovirus
    GraphPad Prism6
    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.

    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.