Anti-SARS-CoV-2 hyperimmune globulin demonstrates potent neutralization and antibody-dependent cellular cytotoxicity and phagocytosis through N and S proteins.

BACKGROUND: Although COVID-19 vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need. METHODS: Functional characterization of anti-SARS-CoV-2 hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus induced cytotoxicity, TCID50 reduction and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA (1), Italy (1), Spain (2): 2 containing the D614G mutation). Neutralization capacity against the original Wuhan SARS-CoV-2 strain and variants (D614G mutant, B.1.1.7, P.1 and B.1.351) was evaluated using a pseudovirus expressing the corresponding spike (S) protein. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated. RESULTS: All SARS-CoV-2 isolates were potently neutralized by hIG as shown by all four methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. hIG induced ADCC and ADCP against SARS-CoV-2 N and S proteins but not E protein. Very low concentrations (25-100 µg IgG/mL) were required. A potent effect was triggered by antibodies in hIG solutions against the SARS-CoV-2 S and N proteins. CONCLUSIONS: Beyond neutralization, IgG Fc-dependent pathways may play a role in combatting SARS-CoV-2 infections using COVID-19 hIG. This could be especially relevant for the treatment of more neutralization-resistant SARS-CoV-2 variants.