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. 2021 Nov 29;16(11):e0259731.
doi: 10.1371/journal.pone.0259731. eCollection 2021.

Modelling the concentration of anti-SARS-CoV-2 immunoglobulin G in intravenous immunoglobulin product batches

Sara Stinca  1 , Thomas W Barnes  1 , Peter Vogel  2 , Wilfried Meyers  2 , Johannes Schulte-Pelkum  3 , Daniel Filchtinski  3 , Laura Steller  3 , Thomas Hauser  1 , Sandro Manni  1 , David F Gardiner  4 , Sharon Popik  4 , Nathan J Roth  1 , Patrick Schuetz  1
Affiliations

Modelling the concentration of anti-SARS-CoV-2 immunoglobulin G in intravenous immunoglobulin product batches

Sara Stinca et al. PLoS One. .

Abstract

Background: Plasma-derived intravenous immunoglobulin (IVIg) products contain a dynamic spectrum of immunoglobulin (Ig) G reactivities reflective of the donor population from which they are derived. We sought to model the concentration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG which could be expected in future plasma pool and final-product batches of CSL Behring's immunoglobulin product Privigen.

Study design and methods: Data was extracted from accessible databases, including the incidence of coronavirus disease 2019 and SARS-CoV-2 vaccination status, antibody titre in convalescent and vaccinated groups and antibody half-life. Together, these parameters were used to create an integrated mathematical model that could be used to predict anti-SARS-CoV-2 antibody levels in future IVIg preparations.

Results: We predict that anti-SARS-CoV-2 IgG concentration will peak in batches produced in mid-October 2021, containing levels in the vicinity of 190-fold that of the mean convalescent (unvaccinated) plasma concentration. An elevated concentration (approximately 35-fold convalescent plasma) is anticipated to be retained in batches produced well into 2022. Measurement of several Privigen batches using the Phadia™ EliA™ SARS-CoV-2-Sp1 IgG binding assay confirmed the early phase of this model.

Conclusion: The work presented in this paper may have important implications for physicians and patients who use Privigen for indicated diseases.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: SS, TB, PV, WM, DG, TH, SM, SP, NR and PS are employees of CSL Behring. JSP, DF and LS are employees of Thermo Fisher Scientific ImmunoDiagnostics Phadia, GmbH.

Figures

Fig 1
Fig 1. Proportions of donor groups and their predicted evolution over time.
Groups 1–3 represent SARS-CoV-2 infection-naïve individuals who had received zero, one or two vaccine doses, respectively. Groups 4–6 represent previously infected individuals who had received zero, one or two vaccine doses, respectively. Actual proportions of donors were calculated up to August 2021, with predicted values estimated from September 2021 until March 2022.
Fig 2
Fig 2. Modelled and measured levels of anti-SARS-CoV-2 IgG in Privigen over time.
(A) Modelled concentrations of anti-SARS-CoV-2 IgG in Privigen batches from January 2021 until August 2022 and (B) modelled (black points) and measured concentrations (blue bars) of anti-SARS-CoV-2 IgG in Privigen batches over time from June 2020 until July 2021. Both absolute (as measured using EliA S1-IgG [left y-axis]), and relative to mean convalescent plasma concentration (MCPC) (right y-axis) are shown. The dotted line in part B indicates a concentration of 81 U/mL, equivalent to one-fold the MCPC.
See this image and copyright information in PMC

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Grants and funding

Funding for this work was provided by CSL Behring AG and Thermo Fisher Scientific ImmunoDiagnostics Phadia GmbH. Editorial assistance was funded by CSL Behring.