Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo

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Abstract

SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.

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  1. SciScore for 10.1101/2020.09.15.298067: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Mouse studies and in vivo infections: All mouse studies were performed at the University of North Carolina (Animal Welfare Assurance #A3410-01) using protocols (19-168, 20-114) approved by the UNC Institutional Animal Care and Use Committee (IACUC).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableTwelve month old female BALB/c mice (Envigo, #047) were inoculated with the indicated concentration of antibody intraperitoneally 12 hours prior to infection.
    Cell Line AuthenticationContamination: All cell lines have been tested negative for contamination with mycoplasma and parental cell lines were obtained from the ATCC.

    Table 2: Resources

    Antibodies
    SentencesResources
    The half-maximal and 90% inhibitory concentrations (IC50 and IC90) for monoclonal antibodies were determined using 4-parameter nonlinear regression (GraphPad Prism).
    IC90
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    For constitutive expression of murine Ace2 (muAce2) in HT1080 cells, a cDNA encoding muAce2 was inserted into a lentiviral vector CSIB 3’ to the SFFV promoter.
    HT1080
    suggested: CLS Cat# 300216/p517_HT-1080, RRID:CVCL_0317)
    HT1080muAce2 cells were generated by transduction with CSIB-based virus followed by selection with 5 μg/ml blasticidin.
    HT1080muAce2
    suggested: None
    For virus titration, the caudal lobe of the right lung was homogenized in PBS, resulting homogenate was serial-diluted and inoculated onto confluent monolayers of Vero E6 cells, followed by agarose overlay.
    Vero E6
    suggested: RRID:CVCL_XD71)
    SARS-CoV-2/SARS-CoV-2 MA pseudotyped reporter virus: SARS-CoV-2 pseudotyped particles were produced by co-transfection of pNL4-3ΔEnv-nanoluc and pSARS-CoV-2-MA-Strunc in 293T cell (Schmidt et al., 2020, Robbiani et al., 2020).
    293T
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Twelve month old female BALB/c mice (Envigo, #047) were inoculated with the indicated concentration of antibody intraperitoneally 12 hours prior to infection.
    BALB/c
    suggested: None
    Software and Algorithms
    SentencesResources
    The half-maximal and 90% inhibitory concentrations (IC50 and IC90) for monoclonal antibodies were determined using 4-parameter nonlinear regression (GraphPad Prism).
    GraphPad
    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.

    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.