Abstract
Analysis of convalescent plasma derived from individuals has shown that IgG3 has the most important role in binding to SARS-CoV-2 antigens; however, this has not yet been confirmed in large studies, and the link between binding and neutralization has not been confirmed. By analyzing plasma pools consisting of 247-567 individual convalescent donors, we demonstrated the binding of IgG3 and IgM to Spike-1 protein and the receptor-binding domain correlates strongly with viral neutralization in vitro. Furthermore, despite accounting for only approximately 12% of total immunoglobulin mass, collectively IgG3 and IgM account for approximately 80% of the total neutralization. This may have important implications for the development of potent therapies for COVID-19, as it indicates that hyperimmune globulins or convalescent plasma donations with high IgG3 concentrations may be a highly efficacious therapy.
Highlights
Coronavirus Disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a pandemic with enormous consequences for patients, public health systems and global economics [1]
In accordance with data reported by Amanat et al [4], we observed a similar distribution of IgG classes in our plasma pools: IgG3 exhibited the highest relative abundance, followed by IgG1
We analyzed large convalescent plasma pools to identify which antibody isotypes/ subclasses bind to three different viral antigens, and most effectively neutralize SARS-CoV-2
Summary
Coronavirus Disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a pandemic with enormous consequences for patients, public health systems and global economics [1]. Neutralizing antibodies have been shown to disrupt the binding of the SARS-CoV-2 surface spike protein to the angiotensin-converting enzyme 2 (ACE2) [3]. Data relating the isotypes and subclasses of the antibodies generated in response to SARS-CoV-2 antigens, and their neutralization capability have not yet been investigated in detail. Amanat et al reported a method to analyze antibodies that can bind the spike protein of the SARS-CoV-2 virus, including immunoglobulin (Ig) sub- and isotype distribution [4]. The development of this assay made serological investigations and large-scale studies
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