Abstract
Understanding the mechanisms involved in long-term persistence of humoral immunity after natural infection or vaccination is challenging and crucial for further research in immunology, vaccine development as well as health policy. Long-lived plasma cells, which have recently been shown to reside in survival niches in the bone marrow, are instrumental in the process of immunity induction and persistence. We developed a mathematical model, assuming two antibody-secreting cell subpopulations (short- and long-lived plasma cells), to analyze the antibody kinetics after HAV-vaccination using data from two long-term follow-up studies. Model parameters were estimated through a hierarchical nonlinear mixed-effects model analysis. Long-term individual predictions were derived from the individual empirical parameters and were used to estimate the mean time to immunity waning. We show that three life spans are essential to explain the observed antibody kinetics: that of the antibodies (around one month), the short-lived plasma cells (several months) and the long-lived plasma cells (decades). Although our model is a simplified representation of the actual mechanisms that govern individual immune responses, the level of agreement between long-term individual predictions and observed kinetics is reassuringly close. The quantitative assessment of the time scales over which plasma cells and antibodies live and interact provides a basis for further quantitative research on immunology, with direct consequences for understanding the epidemiology of infectious diseases, and for timing serum sampling in clinical trials of vaccines.
Highlights
The human adaptive immune response relies on a complex combination of cellular and humoral immunity, mediated by Tand B-lymphocytes
Parameter estimates confirmed the importance of three time scales to explain the decay of antibody levels: the antibodies lifespan, the short-lived plasma cells lifespan and the long-lived plasma cells lifespan
In the absence of replenishment of memory B-cells, this implies that serum antibody titers would be strongly related to the lifespan of antigenspecific plasma cell populations
Summary
The human adaptive immune response relies on a complex combination of cellular and humoral immunity, mediated by Tand B-lymphocytes. Memory B-cells permit a faster and more effective immune response upon further exposures to the antigens, whereas PC are the main antibody-secreting cells (ASC). Different antibody isotopes are present in human sera (IgM, IgA and IgG). They each have relatively limited half-lives, with a maximum of 17.5–26.0 days for Immunoglobulin G (IgG), which represent about 75% of the antibody isotopes in humans [2,3,4]. Exposure to common viral and vaccine antigens has been shown to induce a long-term humoral immune response, which illustrates that improving our understanding of the mechanisms involved in the production and persistence of antibodies remains a (relatively rarely explored) topic of fundamental scientific interest [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
