ABSTRACT
In order to longitudinally track SARS-CoV-2 antibody levels after vaccination or infection, we assessed anti-RBD antibody levels in over 1000 people and found no significant decrease in antibody levels during the first 14 months after infection in unvaccinated participants, however, a significant waning of antibody levels was observed following vaccination. Participants who were pre-immune to SARS-CoV-2 prior to vaccination seroconverted to higher antibody levels, which were maintained at higher levels than in previously infected, unvaccinated participants. Older participants exhibited lower level of antibodies after vaccination, but a higher level after infection than younger people. The rate of antibody waning was not affected by pre-immunity or age. Participants who received a third dose of an mRNA vaccine not only increased their antibody levels ~14-fold, but also had ~3 times more antibodies compared to when they received their primary vaccine series. PBMC-derived memory B cells from 13 participants who lost all circulating antibodies were differentiated into antibody secreting cells (ASCs). There was a significant recall of memory B cell ASCs in the absence of serum antibodies in 5-8 of the 10 vaccinated participants, but not in any of the 3 infected participants, suggesting a strong connection between antibody levels and the effectiveness of memory B cell recall.
ABSTRACT
As the COVID-19 pandemic continues, the authorization of vaccines for emergency use has been crucial in slowing down the rate of infection and transmission of the SARS-CoV-2 virus that causes COVID-19. In order to investigate the longitudinal serological responses to SARS-CoV-2 natural infection and vaccination, a large-scale, multi-year serosurveillance program entitled SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) was initiated at 4 locations in the U.S. The serological assay presented here measuring IgG binding to the SARS-CoV-2 receptor binding domain (RBD) detected antibodies elicited by SARS-CoV-2 infection or vaccination with a 95.5% sensitivity and a 95.9% specificity. We used this assay to screen more than 3100 participants and selected 20 previously infected pre-immune and 32 immunologically naïve participants to analyze their antibody binding to RBD and viral neutralization (VN) responses following vaccination with two doses of either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. Vaccination not only elicited a more robust immune reaction than natural infection, but the level of neutralizing and anti-RBD antibody binding after vaccination is also significantly higher in pre-immune participants compared to immunologically naïve participants (p<0.0033). Furthermore, the administration of the second vaccination did not further increase the neutralizing or binding antibody levels in pre-immune participants (p=0.69). However, ~46% of the immunologically naïve participants required both vaccinations to seroconvert.