Detection of IgM, IgG, IgA and neutralizing antibody responses to SARS-CoV-2 infection and mRNA vaccination

Introduction. One correlate of immunity for coronavirus disease 2019 (COVID-19) is the laboratory detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. These tests are widely implemented for clinical, public health, or research uses.

Hypothesis/Gap Statement. Antibody responses by all classes of immunoglobulins may form from infection and vaccination, but few studies have performed direct head-to-head comparisons between these groups.

Aim. The objective of this study was to evaluate the serological responses in natural SARS-CoV-2 infection and mRNA-based vaccination across multiple immunoglobulin classes and a surrogate neutralizing antibody (NAb) assay.

Methodology. A suite of enzyme-linked immunosorbent assays (ELISAs) was used to qualitatively assess IgA, IgM and IgG positivity and neutralizing per cent signal inhibition of sera from RT-PCR-confirmed SARS-CoV-2-infected patients, COVID-19-immunized individuals ≥2 weeks after a second dose of mRNA vaccine and a set of pre-pandemic negative samples.

Results. For confirmed SARS-CoV-2 infections, seroconversion of IgA, IgM, IgG and NAb increased by week after symptom onset, with positivity reaching 100 % after the third week for every immunoglobulin class. Vaccinated individuals demonstrated 100 % IgG positivity and high per cent signal inhibition by NAb, comparable to natural infection. High specificity, ranging from 96.7–98.9 %, was observed for each assay from a set of pre-pandemic COVID-19-negative samples.

Conclusion. We make use of a comprehensive and readily adoptable suite of serological assays to provide data on the humoral immune response to SARS-CoV-2 infection and vaccination. We found that infection and vaccination both elicit robust IgG, IgM, IgA and neutralizing antibody responses.