Neutralization Of SARS-CoV-2 Variants By A Human Polyclonal Antibody Therapeutic (COVID-HIG, NP-028) With High Neutralizing Titers To SARS-CoV-2
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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).
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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
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: 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 Sentences Resources COVID-HIG is a human hyperimmune product of purified immunoglobulin (IgG) fraction of human plasma containing antibodies to … 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
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: 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 Sentences Resources COVID-HIG is a human hyperimmune product of purified immunoglobulin (IgG) fraction of human plasma containing antibodies to SARS-CoV-2. SARS-CoV-2suggested: NoneEach 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-1/2suggested: (Capricorn Products Cat# HIV-018-48303, RRID:AB_2895202)HCVsuggested: NoneHBV) surface antigen.suggested: NoneExperimental Models: Cell Lines Sentences Resources The test material + virus mixture is added to Vero E6 cells and incubated at 37°C/5% CO2 for 24 hours. Vero E6suggested: NoneSoftware and Algorithms Sentences Resources Titers were calculated using a nonlinear regression curve fit (GraphPad Prism software Inc., La Jolla, CA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)) (Prism, Graphpad). Graphpadsuggested: (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:
Identifier Status Title NCT04546581 Completed Inpatient Treatment of COVID-19 With Anti-Coronavirus Immuno… NCT04910269 Recruiting Outpatient 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.
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