Neutralization Of SARS-CoV-2 Variants By A Human Polyclonal Antibody Therapeutic (COVID-HIG, NP-028) With High Neutralizing Titers To SARS-CoV-2

  1. Derek Toth

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Since the start of the COVID-19 outbreak the World Health Organization (WHO) has classified multiple SARS-CoV-2 Variants-of-Concern and Variants-of-Interest (VOC/VOI) with mutations in their Spike protein that increase transmissibility and/or reduce the effectiveness of vaccines and monoclonal antibody therapeutics. The emergence of these variants represents a significant health risk and highlights the need for additional COVID-19 therapeutics that maintain the ability to neutralize current, as well as future variants.

COVID-HIG (NP-028) is a polyclonal Anti-SARS-CoV-2 human Immunoglobulin purified from source human plasma screened for high antibody titers to SARS-CoV-2 antigens. COVID-HIG was previously evaluated in INSIGHT 013 clinical trial [ NCT04546581 ] which was an international, multi-center, adaptive, randomized, double-blind, placebo-controlled trial of the safety, tolerability and efficacy of a single dose infusion (up to 400 mL) of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin (hIVIG) for the treatment of adult recently hospitalized COVID-19 patients (N=593). COVID-HIG is currently being evaluated for clinical efficacy in a Phase 3 placebo-controlled study INSIGHT 012 ( NCT04910269 ) to compare the safety and efficacy of a single infusion of anti-COVID-19 hyperimmune immunoglobulin (hIVIG) versus placebo among adults with recently diagnosed SARS-CoV-2 infection who do not require hospitalization.

In the present study, in-vitro pseudovirus and live virus neutralization assays were used to assess the impact of SARS-CoV-2 variant spike mutations on neutralizing potency of COVID-HIG. These assays are valuable tools for monitoring the potential impact of variant mutations on efficacy of antibody therapeutics as well as vaccines/natural immunity.

To date, COVID-HIG (NP-028) has been shown to retain neutralizing potency against 20 full spike protein sequence SARS-CoV-2 pseudovirus variants including all currently classified VOC/VOI (Alpha, Beta, Gamma, Delta/Delta+, Eta, Iota, Kappa, Lambda, Mu as of Sept 2021) as well as 4 live virus variants (Alpha, Beta, Gamma, and Iota).

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2022.01.27.478053: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationAuthentication: COVID-HIG activity against SARS-CoV-2 is determined by validated in-house potency assays (trimeric SARS-CoV-2 Spike protein antigen and Lentivirus neutralization) at product release and has been characterized for neutralizing potency by a wild-type SARS-CoV-2 assay (Bennett et al., 2021) as well Production of SARS-CoV-2 Pseudovirus Variants and Neutralization

    Table 2: Resources

    Antibodies
    SentencesResources
    COVID-HIG is a human hyperimmune product of purified immunoglobulin (IgG) fraction of human plasma containing antibodies to SARS-CoV-2.
    SARS-CoV-2
    suggested: None
    Each plasma donation is tested for human immunodeficiency viruses 1/2 (HIV-1/2) and hepatitis C virus (HCV) antibodies, and as well as hepatitis B virus (HBV) surface antigen.
    HIV-1/2
    suggested: (Capricorn Products Cat# HIV-018-48303, RRID:AB_2895202)
    HCV
    suggested: None
    HBV) surface antigen.
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The test material + virus mixture is added to Vero E6 cells and incubated at 37°C/5% CO2 for 24 hours.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Titers were calculated using a nonlinear regression curve fit (GraphPad Prism software Inc., La Jolla, CA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    ) (Prism, Graphpad).
    Graphpad
    suggested: (GraphPad, RRID:SCR_000306)

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04546581CompletedInpatient Treatment of COVID-19 With Anti-Coronavirus Immuno…
    NCT04910269RecruitingOutpatient Treatment With Anti-Coronavirus Immunoglobulin

    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.
    • No funding statement was detected.
    • 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 10.1101/2022.01.27.478053v1 on bioRxiv