Antibody Responses to BNT162b2 Vaccination in Japan: Monitoring Vaccine Efficacy by Measuring IgG Antibodies against the Receptor-Binding Domain of SARS-CoV-2.

To fight severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), mass vaccination has begun in many countries. To investigate the usefulness of a serological assay to predict vaccine efficacy, we analyzed the levels of IgG, IgM, and IgA against the receptor-binding domain (RBD) of SARS-CoV-2 in the sera from BNT162b2 vaccinated individuals in Japan. This study included 219 individuals who received two doses of BNT162b2. The levels of IgG, IgM, and IgA against RBD were measured by enzyme-linked immunosorbent assay before and after the first and second vaccination, respectively. The relationship between antibody levels and several factors, including age, gender, and hypertension were analyzed. Virus-neutralizing activity in sera was measured to determine the correlation with the levels of antibodies. A chemiluminescent enzyme immunoassay (CLEIA) method to measure IgG against RBD was developed and validated for the clinical setting. The levels of all antibody isotypes were increased after vaccination. Among them, RBD-IgG was dramatically increased after the second vaccination. The IgG levels in females were significantly higher than in males. There was a negative correlation between age and IgG levels in males. The IgG levels significantly correlated with the neutralizing activity. The CLEIA assay measuring IgG against RBD showed a reliable performance and a high correlation with neutralizing activity. Monitoring of IgG against RBD is a powerful tool to predict the efficacy of SARS-CoV-2 vaccination and provides useful information in considering a personalized vaccination strategy for COVID-19. IMPORTANCE Mass vaccination campaigns using mRNA vaccines against SARS-CoV-2 have begun in many countries. Serological assays to detect antibody production may be a useful tool to monitor the efficacy of SARS-CoV-2 vaccination in individuals. Here, we reported the induction of antibody isotype responses after the first and second dose of the BNT162b2 vaccine in a well-defined cohort of employees in Japan. We also reported that age, gender, and hypertension are associated with differences in antibody response after vaccination. This study not only provides valuable information with respect to antibody responses after BNT162b2 vaccination in the Japanese population but also the usefulness of serological assays for monitoring vaccine efficacy in clinical laboratories to determine a personalized vaccination strategy for COVID-19.

Comparative Analysis of Antigen-Specific Anti-SARS-CoV-2 Antibody Isotypes in COVID-19 Patients.

Serological tests for detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Abs in blood are expected to identify individuals who have acquired immunity against SARS-CoV-2 and indication of seroprevalence of SARS-CoV-2 infection. Many serological tests have been developed to detect Abs against SARS-CoV-2. However, these tests have considerable variations in their specificity and sensitivity, and whether they can predict levels of neutralizing activity is yet to be determined. This study aimed to investigate the kinetics and neutralizing activity of various Ag-specific Ab isotypes against SARS-CoV-2 in serum of coronavirus disease 2019 (COVID-19) patients confirmed via PCR test. We developed IgG, IgM, and IgA measurement assays for each Ag, including receptor-binding domain (RBD) of spike (S) protein, S1 domain, full-length S protein, S trimer, and nucleocapsid (N) domain, based on ELISA. The assays of the S protein for all isotypes showed high specificity, whereas the assays for all isotypes against N protein showed lower specificity. The sensitivity of all Ag-specific Ab isotypes depended on the timing of the serum collection and all of them, except for IgM against N protein, reached more than 90% at 15-21 d postsymptom onset. The best correlation with virus-neutralizing activity was found for IgG against RBD, and levels of IgG against RBD in sera from four patients with severe COVID-19 increased concordantly with neutralizing activity. Our results provide valuable information regarding the selection of serological test for seroprevalence and vaccine evaluation studies.