Isotyping and Quantitation of the Humoral Immune Response to SARS-CoV-2

Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS-CoV-2 positive plasma samples tested exhibited significant neutralization capacity using a surrogate virus neutralization assay. Of the IgG subclasses, IgG1 and IgG3 exhibited the highest viral neutralization capacity; whereas, IgG2 and IgG4 viral neutralization was not observed. Comparison of SARS-CoV-2 elicited total IgG binding to emerging variant (alpha, beta, and delta) RBDs indicated decreased binding. Furthermore, neutralization by SARS-CoV-2 convalescent plasma of delta and omicron variant RBDs was significantly decreased suggesting that neutralizing antibodies in convalescent plasma are less effective in inhibiting variants currently in circulation.