Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/13612
Title: Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus
Authors: Andraud, Mathieu
Lejeune, Olivier
Musoro, Jammbe Z.
OGUNJIMI, Benson 
Beutels, Philippe
HENS, Niel 
Issue Date: 2012
Publisher: PUBLIC LIBRARY SCIENCE
Source: PLOS COMPUTATIONAL BIOLOGY, 8 (3) (Art N° e1002418)
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.
Notes: [Andraud, Mathieu; Lejeune, Olivier; Ogunjimi, Benson; Beutels, Philippe; Hens, Niel] Univ Antwerp, Vaccine & Infect Dis Inst VAXINFECTIO, Ctr Hlth Econ Res & Modelling Infect Dis CHERMID, B-2020 Antwerp, Belgium. [Lejeune, Olivier] Univ Dundee, SYMBIOS Ctr, Div Math, Dundee, Scotland. [Musoro, Jammbe Z.; Hens, Niel] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat, Diepenbeek, Belgium. [Musoro, Jammbe Z.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
Keywords: Biochemical Research Methods; Mathematical & Computational Biology
Document URI: http://hdl.handle.net/1942/13612
ISSN: 1553-734X
e-ISSN: 1553-7358
DOI: 10.1371/journal.pcbi.1002418
ISI #: 000302244000026
Rights: 2012 Andraud et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Category: A1
Type: Journal Contribution
Validations: ecoom 2013
Appears in Collections:Research publications

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