PB0609 - Plasma Fractionation by HaemaFrac® Technology - A Bioprocessing Innovation

Background: Conferring passive immunity to emerging SARS-CoV-2 variants using monoclonal antibodies (mAbs) has also proven ineffectual, with the FDA recently revoking authorization of bebtelovimab. Alternatively, pooled COVID-19 Convalescent Plasma (CP) contains a broad spectrum of polyclonal antibodies, representative of a collective immune response to SARS-CoV-2 prevailing variants. Aegros has developed an innovative tangential flow electrophoresis-based plasma fractionation technology, HaemaFrac®(Fig.1), that isolates plasma proteins based on size and charge. Using HaemaFrac®, IgG was purified from pooled CP, producing anti-SARS-CoV-2 hyperimmune immunoglobulin (hIVIg), CovImmuneTM, to provide passive immunity during the COVID-19 pandemic.

Aims: Production of an anti-SARS-CoV-2 hIVIg preparation by HaemaFrac® technology.

Methods: IgG was fractionated from pooled COVID-19 CP by HaemaFrac® Technology, whereby initially, CP flows tangentially over a proprietary separation membrane within a stream (Stream 1). Upon application of a potential difference, target proteins of interest cross the membrane, driven by electromotive force into the product stream (Stream 2). Central to the HaemaFrac® bioprocess is the separation cartridge system, whereby membranes are stacked within a cartridge module.

Results: Haemafrac® achieved highly effective separation of immunoglobulins from CP. Compared to Cohn plasma fractionation, based on cold ethanol fractionation, higher product yields were obtained using Haemafrac®, thereby allowing for efficient use of a finite resource of donor plasma. In the clinical context, the obtention of CovImmuneTM, a highly potent anti-SARS-CoV-2 hyperimmune IVIG preparation, retains IgG subclass distribution to source CP while maintaining physiological levels of IgG3 (traditionally lost in Cohn Fractionation)- an important anti-viral effector IgG Subclass.

Conclusion(s): HaemaFrac® technology, which has many applications in plasma fractionation, has successfully provided a clinical grade hIVIg preparation CovImmuneTM, now undergoing clinical trial, for conferring passive immunity to SARS-CoV-2. The polyclonal CovImmuneTM has therapeutic advantages over CP and mAbs, providing broader coverage of SARS-CoV-2 variants and their neutralization.