The optimal way to measure immunity to SARS-CoV-2
Several serologic assays are available for detecting antibody responses to SARS-CoV-2 infection; however, their sensitivity and specificity are limited and their correlation with viral neutralisation (considered a marker of protective immunity) is unclear, thereby obscuring their interpretation. To examine this issue, researchers assessed antibody levels as detected by enzyme-linked immunosorbent assay (ELISA) of four viral antigens (the receptor-binding domain [RBD], the spike protein, UV-inactivated SARS-CoV-2 virus, and the nucleocapsid protein [NP]), followed by a standard viral neutralisation assay. Plasma from 15 individuals who had symptomatic COVID-19 and who were enrolled around 21 days after their positive PCR test were compared with 30 negative blood-bank samples obtained prior to December 2019.
Using criteria of high specificity, negative predictive value, low misidentification of subjects, and strong agreement with the plaque reduction neutralisation test, ELISAs for RBD IgG, spike protein IgG3, and NP IgG all performed well — with the ELISA for spike protein IgG3 performing best. This small study employed viral neutralisation testing as a benchmark to measure the sensitivity and specificity of several antibody assays involving different SARS-CoV-2 antigens. Among these, the ELISA for the spike protein IgG3 was optimal.
The authors suggest that this assay could be followed by a viral neutralisation assay to more fully assess protective immunity.
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