Production of anti‐SARS‐CoV‐2 hyperimmune globulin from convalescent plasma

Abstract

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].

Anti-SARS-CoV-2 hyperimmune immunoglobulin provides potent and robust neutralization capacity and antibody-dependent cellular cytotoxicity and phagocytosis induction through N and S proteins

“…Potentially accompanying impurity proteins (IgM, IgA, and anti-A, anti-B and anti-D antibodies) are reduced to minimal levels. Further details of hIG characteristics are available elsewhere [7].…”

“…A minimum of 16,000 cells are counted per sample dilution across four wells -two each in duplicate plates. Data are reported based on a 4-parameter regression curve (using a constrained fit) as a 50% neutralization titer (half maximal inhibitory dilution : ID50) [7,19].…”

Convalescent plasma to treat COVID-19: Following the Argentinian lead

“…passive antibody administration to suppress viral replication, has been heralded as a potential treatment breakthrough [7]. Such immunotherapy encompasses polyclonal antibodies contained in plasma donations from COVID-19 convalescent patients to be transfused as such [8,9], or as hyperimmune globulin (hIVIG) after pooling and fractionation [10], and anti-SARS-CoV-2 monoclonal antibodies (MoAbs) of human or animal origin [11].…”

“…Anti-SARS-CoV-2 hyperimmune globulin (HyperIg) has been prepared in several locations worldwide and is currently undergoing clinical evaluation [10]. As with convalescent plasma, the polyclonal nature of antibodies in HyperIg may be advantageous with regard to variant immune-selection.…”

“…Of note however, is the absence of IgM and IgA in HyperIg. Anti-SARS-CoV-2 IgM and IgA may be contributive to antiviral efficacy with the anti-SARS-CoV-2 IgG [10,17].…”