Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma

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Abstract

BACKGROUND

In late 2019, the SARS-CoV-2 virus emerged in China and quickly spread into a world-wide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti-SARS-CoV-2 hyperimmune globulin (hIVIG).

STUDY DESIGN AND METHODS

Convalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small-scale facility designed and built to rapidly address emerging infectious diseases.

RESULTS

Processing convalescent plasma into hIVIG resulted in a highly purified IgG product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG antibody specific to SARS-CoV-2 were increased over 10-fold from convalescent plasma to the final product. Normalized ELISA activity (per mg/mL IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti-A, anti-B and anti-D antibodies) were reduced to minimal levels.

CONCLUSIONS

Multiple batches of anti-SARS-CoV-2 hyperimmune globulin (hIVIG) that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) [ NCT04546581 ].

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  1. SciScore for 10.1101/2020.11.18.388991: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Asymptomatic donors tested only by an anti-SARS-CoV-2 antibody test were required to wait seven days prior to donation, but could donate immediately if they had a negative NAT.
    anti-SARS-CoV-2
    suggested: None
    Donors also had to be negative for human leukocyte antigen (HLA) antibodies.
    human leukocyte antigen (HLA)
    suggested: None
    Software and Algorithms
    SentencesResources
    10 All donations were tested by NAT (Procleix SARS-CoV-2 assay, Grifols Diagnostic Systems, Emeryville, CA) to confirm absence of SARS-CoV-2 infection and by serology to confirm presence of anti-SARS-COV-2 IgG (Architect SARS-CoV-2 IgG assay, Abbott Ireland, Diagnostics Division, Finisklin Business Park, Sligo, Ireland or Recombivirus Human Anti-SARS-CoV-2 Virus Spike 1 IgG ELISA Kit, Alpha Diagnostic International, San Antonio, TX).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)

    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
    NCT04546581Active, not recruitingInpatient Treatment With Anti-Coronavirus Immunoglobulin (IT…


    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.