Production of Hyperimmune Anti-SARS-CoV-2 Intravenous Immunoglobulin from Pooled COVID-19 Convalescent Plasma

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 (NCT 04521309).

Keywords::

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

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/imt-2020-0263

Author Contributions

S Ali was responsible for concept design, supervision, laboratory experimentation, critical analysis and drafting and finalization of the manuscript. S Uddin was responsible for process design optimization, laboratory experimentation, critical analysis and drafting and finalization of the manuscript. A Ali performed process quality control, laboratory experimentation, critical analysis and drafting and finalization of the manuscript. M Khan performed process quality control, laboratory experimentation, critical analysis and drafting of the manuscript. F Anjum and R Ali performed process design optimization, laboratory experimentation and critical analysis. E Shalim carried out laboratory experimentation, data acquisition and critical analysis. I Ahmed and U Bukhari performed laboratory experimentation and drafting of the manuscript. S Muhaymin performed laboratory experimentation and critical analysis. S Luxmi was responsible for the collection of raw material and addressed clinical needs. A Khan provided expert advice and was responsible for process design approval and finalization of the manuscript. S Quraishy was responsible for concept design, process design approval and finalization of the manuscript.

Financial & competing interests disclosure

The authors received funding from Dow University of Health Sciences and Higher Education Commission Pakistan grant number: 20-RRG-134/RGM/R&D/HEC/2020. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval for animal experimental investigations. Ref IRB-1685/DUHS/Approval/2020/79. The animals used in this study were maintained in accordance to the ethical guidelines of Dow University of Health Sciences, Karachi, Pakistan.

Additional information

Funding

The authors received funding from Dow University of Health Sciences and Higher Education Commission Pakistan grant number: 20-RRG-134/RGM/R&D/HEC/2020. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.