TY - JOUR
T1 - Living on Three Time Scales
T2 - The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus
AU - Andraud, Mathieu
AU - Lejeune, Olivier
AU - Musoro, Jammbe Z.
AU - Ogunjimi, Benson
AU - Beutels, Philippe
AU - Hens, Niel
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pcbi.1002418
DO - 10.1371/journal.pcbi.1002418
M3 - Article
C2 - 22396639
SN - 1553-734X
VL - 8
SP - -
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 3
M1 - e1002418
ER -