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. 2021 Apr;13(5):397-407.
doi: 10.2217/imt-2020-0263. Epub 2021 Feb 9.

Production of hyperimmune anti-SARS-CoV-2 intravenous immunoglobulin from pooled COVID-19 convalescent plasma

Shaukat Ali  1   2 , Syed M Uddin  1 , Ayesha Ali  1 , Fatima Anjum  2 , Rashid Ali  1 , Elisha Shalim  1 , Mujtaba Khan  1 , Iqra Ahmed  1 , Sheikh M Muhaymin  1 , Uzma Bukhari  3 , Shobha Luxmi  4 , Abdul S Khan  5 , Saeed Quraishy  6
Affiliations

Production of hyperimmune anti-SARS-CoV-2 intravenous immunoglobulin from pooled COVID-19 convalescent plasma

Shaukat Ali et al. Immunotherapy. 2021 Apr.

Abstract

Background: This study assesses the feasibility of producing hyperimmune anti-COVID-19 intravenously administrable immunoglobulin (C-IVIG) from pooled convalescent plasma (PCP) to provide a safe and effective passive immunization treatment option for COVID-19. Materials & methods: PCP was fractionated by modified caprylic acid precipitation followed by ultrafiltration/diafiltration to produce hyperimmune C-IVIG. Results: In C-IVIG, the mean SARS-CoV-2 antibody level was found to be threefold (104 ± 30 cut-off index) that of the PCP (36 ± 8.5 cut-off index) and mean protein concentration was found to be 46 ± 3.7 g/l, comprised of 89.5% immunoglobulins. Conclusion: The current method of producing C-IVIG is feasible as it uses locally available PCP and simpler technology and yields a high titer of SARS-CoV-2 antibody. The safety and efficacy of C-IVIG will be evaluated in a registered clinical trial (NCT04521309).

Keywords: SARS-CoV-2; anti-COVID-19 IVIG; caprylic acid; convalescent plasma; diafiltration; immunotherapy; intravenous immunoglobulins; passive immunization; pooled plasma; ultrafiltration.

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Figures

Figure 1.
Figure 1.. Process flow diagram for the production of high-titer anti-SARS-CoV-2 intravenously administrable immunoglobulin.
IVIG: Intravenously administrable immunoglobulin.
Figure 2.
Figure 2.. Immunoglobulin content and anti-SARS-CoV-2 antibody level.
(A) Comparison of mean IgG, IgM, IgA and anti-SARS-CoV-2 antibody levels in pooled convalescent plasma with that in C-IVIG and control IVIG produced by the caprylic acid precipitation method. Control IVIG (pre-pandemic) was found to be nonreactive for SARS-CoV-2 antibodies. The anti-SARS-CoV-2 antibody level is measured as cut-off index (sample absorbance/cut-off; cut-off = 1). (B) Comparison of IgG, IgM and IgA content (as percentage of total immunoglobulin) in pooled plasma, C-IVIG and control IVIG. (C) Mean percentage yield of IgG, IgA, IgM and anti-SARS-CoV-2 antibodies from convalescent plasma fractionation. All values are represented as the mean of eight consecutive batches of C-IVIG production. C-IVIG: Anti-COVID-19 intravenously administrable immunoglobulin; IVIG: Intravenously administrable immunoglobulin.
Figure 3.
Figure 3.. SDS-PAGE.
Patterns of eight consecutive batches of IVIG in (A) non-reducing and (B) reducing conditions. B1–B8: Batch numbers; IVIG: Intravenously administrable immunoglobulin; Mw.M: Molecular weight markers (10–250 KDa).
Figure 4.
Figure 4.. Histological examination of liver and kidney of rats.
(A) Cross-section of kidney treated with 0.5 mg/kg dose of intravenously administrable immunoglobulin. (B) Cross-section of liver treated with 0.5 mg/kg dose. (C) Cross-section of kidney of control group. (D) Cross-section of liver of control group.
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