Michael T White1, Jamie T Griffin1, Onome Akpogheneta2, David J Conway2, Kwadwo A Koram3, Eleanor M Riley4, Azra C Ghani1. 1. Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modelling, Imperial College London. 2. Department of Pathogen Molecular Biology Medical Research Council Laboratories, Fajara, Gambia. 3. Noguchi Memorial Institute for Medical Research, University of Ghana, Legon. 4. Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, United Kingdom.
Abstract
BACKGROUND: Acquired immune responses to malaria have widely been perceived to be short-lived, with previously immune individuals losing immunity when they move from malaria-endemic areas. However long-lived Plasmodium falciparum-specific antibody responses lasting for an individual's lifetime are frequently observed. METHODS: We fit mathematical models of the dynamics of antibody titers to P. falciparum antigens from longitudinal cohort studies of African children to estimate the half-lives of circulating immunoglobulin G (IgG) antibodies and IgG antibody-secreting cells (ASCs). RESULTS: Comparison of antibody responses in the younger Ghanaian cohort and the older Gambian cohort suggests that young children are less able to generate the long-lived ASCs necessary to maintain the circulating antibodies that may provide protection against reinfection. Antibody responses in African children can be described by a model 15 including both short-lived ASCs (half-life range, 2-10 days), which are responsible for boosting antibody titers following infection, and long-lived ASCs (half-life range, 3-9 years), which are responsible for maintaining sustained humoral responses. CONCLUSIONS: The rapid decay of antibodies following exposure to malaria and the maintenance of sustained antibody responses can be explained in terms of populations of short-lived and long-lived ASCs.
BACKGROUND: Acquired immune responses to malaria have widely been perceived to be short-lived, with previously immune individuals losing immunity when they move from malaria-endemic areas. However long-lived Plasmodium falciparum-specific antibody responses lasting for an individual's lifetime are frequently observed. METHODS: We fit mathematical models of the dynamics of antibody titers to P. falciparum antigens from longitudinal cohort studies of African children to estimate the half-lives of circulating immunoglobulin G (IgG) antibodies and IgG antibody-secreting cells (ASCs). RESULTS: Comparison of antibody responses in the younger Ghanaian cohort and the older Gambian cohort suggests that young children are less able to generate the long-lived ASCs necessary to maintain the circulating antibodies that may provide protection against reinfection. Antibody responses in African children can be described by a model 15 including both short-lived ASCs (half-life range, 2-10 days), which are responsible for boosting antibody titers following infection, and long-lived ASCs (half-life range, 3-9 years), which are responsible for maintaining sustained humoral responses. CONCLUSIONS: The rapid decay of antibodies following exposure to malaria and the maintenance of sustained antibody responses can be explained in terms of populations of short-lived and long-lived ASCs.
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