The Effect of Waning on Antibody Levels and Memory B Cell Recall following SARS-CoV-2 Infection or Vaccination

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.

SARS‐CoV‐2 antibody dynamics over time and risk factors associated with infection and long COVID‐19 symptoms in large working environments

“…This meant that individuals generating a low starting level lost detectable antibodies after approximately 6 months. It is important to note that waning of humoral immunity following infection versus the one following vaccination is still debated, and the results are diverging [25–27]. Additionally, we observed increased antibody levels postvaccination in individuals infected prior to vaccination compared to vaccinated infection naïve individuals, agreeing with existing knowledge on increasing antibody titers in individuals with hybrid immunity [12, 28, 29].…”

Non-cross-reactive epitopes dominate the humoral immune response to COVID-19 vaccination – kinetics of plasma antibodies, plasmablasts and memory B cells

“…revealed an initial decline in S1-specific class-switched Bmem frequencies after a 2 nd COVID-19 vaccination, followed by a stabilization for the next 8 months ( 16 ). A similar antibody waning was also observed after the 3 rd dose ( 16 , 17 ), emphasizing that these kinetics mirror the dynamics of a typical immune response following vaccination.…”

Prior SARS-CoV-2 Infection Enhances Initial mRNA Vaccine Response with a Lower Impact on Long-Term Immunity

“…In 2020, the SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) program, funded by the U.S. National Institutes of Health, was initiated to understand the immune responses elicited following infection with SARS-CoV-2 and/or vaccination against COVID-19. Participants between 22 and 65 y of age were enrolled starting in October 2020 with written informed consent in Athens and Augusta, GA, Memphis, TN, or Los Angeles, CA ( 27 , 28 ). The study procedures, informed consent, and data collection documents were reviewed and approved by the WIRB Copernicus Group Institutional Review Board (approval no.…”

“…The study procedures, informed consent, and data collection documents were reviewed and approved by the WIRB Copernicus Group Institutional Review Board (approval no. 202029060) ( 27 , 29 ). Forty individuals were identified as “SARS-CoV-2–naive” (no SARS-CoV-2 infection before vaccination) or “prior COVID” (previous SARS-CoV-2 infection before vaccination) based on Ag test (PCR), self-reporting, and/or anti–receptor-binding domain (RBD) Ab levels.…”