Background In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus emerged in China and quickly spread into a worldwide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti‐SARS‐CoV‐2 hyperimmune globulin (hIVIG). Study Design and Methods Convalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small‐scale facility designed and built to rapidly address emerging infectious diseases. Results Processing convalescent plasma into hIVIG resulted in a highly purified immunoglobulin G (IgG) product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG specific to SARS‐CoV‐2 were increased over 10‐fold from convalescent plasma to the final product. Normalized enzyme‐linked immunosorbent assay activity (per mg/ml IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti‐A, anti‐B, and anti‐D) were reduced to minimal levels. Conclusions Multiple batches of anti‐SARS‐CoV‐2 hIVIG that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti‐Coronavirus Immunoglobulin (ITAC) [NCT04546581].

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BACKGROUNDIn late 2019, the SARS-CoV-2 virus emerged in China and quickly spread into a world-wide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti-SARS-CoV-2 hyperimmune globulin (hIVIG).STUDY DESIGN AND METHODSConvalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small-scale facility designed and built to rapidly address emerging infectious diseases.RESULTSProcessing convalescent plasma into hIVIG resulted in a highly purified IgG product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG antibody specific to SARS-CoV-2 were increased over 10-fold from convalescent plasma to the final product. Normalized ELISA activity (per mg/mL IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti-A, anti-B and anti-D antibodies) were reduced to minimal levels.CONCLUSIONSMultiple batches of anti-SARS-CoV-2 hyperimmune globulin (hIVIG) that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) [NCT04546581].

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.