Persistent antibody clones dominate the plasma antibody repertoire

The half-life of therapeutic monoclonal antibodies has been extensively studied, and has been found to range roughly between one and four weeks. In contrast, it has been reported that, for instance, viral antigen recognition in blood is extremely durable. Until recently, it was not possible to determine whether the sustained immune response resulted from ongoing production of identical clones, or if repeated activation of B cells led to the continuous emergence of new clones over time. We have developed mass spectrometry-based methods to analyze the antibody repertoire with clonal resolution. Initial analyses conducted on samples from severely ill patients over a period of up to 60 days demonstrated substantial changes in the antibody repertoire over time for some clones, while other clones exhibited remarkable stability.

In this study, we examined the clonal repertoire stability in healthy individuals over a longer time period. We followed eleven healthcare workers for almost one year during which they did not experience any significant illness. However, they did receive three doses of a COVID-19 vaccine. Blood samples were collected at nine timepoints, and the plasma IgG1 antibody repertoire was recorded using Fab clonal profiling by mass spectrometry.

We show that the plasma IgG1 repertoires of healthy donors are dominated by a few clones, and that these clones remain remarkably stable over at least one year. Even after administering three doses of the COVID-19 vaccine the detected repertoire remained mostly unchanged. This suggests that this large portion of the total repertoire associates with long term immunity, rather than acute infections. Moreover, given that these dominant clones do not appear to undergo affinity maturation, it is most likely that they are produced by long-lived rather than short-lived plasma cells.