The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged from Wuhan, China, in late 2019 and rapidly spread across the world, progressing into a full-blown pandemic. Since it is a novel virus, scientists worldwide immediately started working on developing a vaccine or effective therapeutic agents to fight SARS-CoV-2.
The use of convalescent plasma in the treatment of infectious diseases
Convalescent plasma has now been identified as a potential treatment option for coronavirus disease (COVID-19). Convalescent plasma has been used in the past to treat infectious diseases, for example, during the Spanish flu pandemic and the more recent SARS and the Middle East respiratory syndrome (MERS) outbreaks.
Although convalescent plasma has some disadvantages, such as the variations in nature and the neutralizing power of the antibodies in the plasma from one donor to another, many can be overcome by purification and concentration of the antibodies into drug preparations. Human immunoglobulin-based products derived from pooled plasma of convalescent or vaccinated donors have been used for several years in treating various infectious diseases.
Purifying convalescent plasma to produce anti-SARS-CoV-2 hyperimmune globulin
In a recent study published in the preprint server bioRxiv*, researchers from the Grifols Bioscience Research Group reported on the collection of convalescent plasma and production of anti-SARS-CoV-2 hyperimmune globulin for use in clinical research.
The researchers collected convalescent plasma from donors part of an existing network of plasma donation centers. The hyperimmune globulin was manufactured using a caprylate/chromatography purification process. Initial batches of the anti-SARS-CoV-2 hyperimmune globulin or hIVIG were produced in a small-scale facility built specifically to address emerging infectious diseases.
Processing of convalescent plasma resulted in a highly purified IgG product with concentrated neutralizing antibody activity. Thus, this hyperimmune globulin makes it possible to administer higher antibody activity per unit of volume with lesser potential for adverse reactions associated with plasma administration.
The final product had over 10-fold SARS-CoV-2-specific IgG antibody
In the process of purification of convalescent plasma into the final product, the IgG concentration and SARS-CoV-2-specific IgG antibody increased more than 10-fold. Antibody neutralizing activity increased nearly 3-fold from the plasma pool to the final hyperimmune globulin. This 3-fold increase in neutralizing activity is smaller than expected based on ELISA titer, which the authors think might be because of missing contributions from IgA and IgM removed during IgG purification. Normalized ELISA activity was maintained during the entire process.
“Antibody neutralizing activity was increased approximately three-fold from the plasma pool to the final product.”
In the final product batches, the protein content was 100% IgG with 98% monomer and dimer forms. The levels of potentially hazardous proteins such as IgM, IgA, and anti-A, anti-B and anti-D antibodies were minimized as much as possible. Thus, the authors report that they successfully produced multiple batches of anti-SARS-CoV-2 hyperimmune globulin from human convalescent plasma and the hIVIG produced satisfied regulatory requirements.
Anti-SARS-CoV-2 hyperimmune globulin has more diverse antibodies with broader anti-viral activity
A potential advantage of this anti-SARS-CoV-2 hyperimmune globulin over direct administration of plasma from donors is the diversity of antibodies acquired from a pool of convalescent donors. These diverse antibodies may offer a much broader range of anti-viral activity by targeting multiple viral epitopes and recruiting different cellular mechanisms. The authors believe that this diversity may also be important in terms of overcoming viral mutations.
“A potential advantage hIVIG over direct administration of plasma from individuals or a monoclonal antibody is the diversity of antibodies obtained from a pool of convalescent donors which may provide a wider range of anti-viral activity.”
Overall, the processes described in this study resulted in the production of multiple batches of anti-SARS-CoV-2 hyperimmune globulin that met all regulatory requirements. Moreover, previous experience with hyperimmune globulin products used in the treatment of tetanus, rabies, and hepatitis B offers a reasonable expectation for the safety and efficacy of anti-SARS-CoV-2 hyperimmune globulin.
Clinical trials have been initiated to analyze the efficacy of this hyperimmune globulin. The Inpatient Treatment with AntiCoronavirus Immunoglobulin (ITAC) trial is the first clinical study in which the hyperimmune globulin is being evaluated.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.