PB0074 - Hyper-immunoglobulin- CovImmuneTM, provides a broader coverage against diverse SARS-CoV-2 variants relevant to the COVID-19 pandemic

Background: Mutations thwart the effectiveness of monoclonal antibodies against SARS-CoV-2 in the Spike protein variants that intersect with the binding epitopes of mAbs. Thus, polyclonal convalescent plasma (CP) and hyperimmune immunoglobulin (hIgG) offer the best alternative for transferring passive immunity and reducing disease severity and mortality in COVID-19 patients. Using HaemaFrac® (Aegros), a clinical grade CovImmuneTM- an hIgG for human use was developed at scale from pooled CP. While the clinical trial is underway, we discuss the neutralization capability of its various batches against diverse SARS-CoV-2 variants.

Aims: Evaluate the viral neutralization capability of CovImmuneTM against SARS-CoV-2 variants- and compare with CP.

Methods: Plasma from men and nulliparous women convalescent for COVID-19 was collected and pooled, and the purified hIVIG was fractionated from pooled convalescent plasma on HaemaFrac® developed by Aegros. Viral neutralization efficacy of Lifeblood plasma for infusion, pooled plasma for manufacture, and CoVimmune (batches #056, #122, #147, #183) was tested against SARS-CoV-2 Ancestral Clade A, Delta, and Omicron (BA.2 and BA.5) variants using clinical isolates in a high content neutralization assay.

Results: Haemafrac® effectively separated polyclonal IgG from pooled plasma with an increase in the level of anti-spike IgG by up to 9-fold. Potency was enriched towards Clade A and Delta Pre-Omicron variants, although increasing breadth was observed for Omicron variants (BA.2 and BA.5) of SARS-CoV-2. This was in the context of early pandemic plasma samples. Unlike mAbs, plasma donations will mature over time and be subject to future bivalent booster rollout benefits. Thus, the benefits of CovimmuneTM retaining the IgG subclass distribution during the separation process are highlighted here (Fig.1).

Conclusion(s): Retention of IgG subclass distribution in CovimmuneTM provided significant advantages in broader viral neutralization capability while minimizing viral escape compared to mAbs. A clinical trial at Aegros will show if it effectively blocks viral entry and infection.