Abstract
BackgroundNaturally-acquired antibody responses to antigens on the surface of Plasmodium falciparum-infected red blood cells (iRBCs) have been implicated in antimalarial immunity. To profile the development of this immunity, we have been studying a cohort of Malian children living in an area with intense seasonal malaria transmission.Methodology/Principal FindingsWe collected plasma from a sub-cohort of 176 Malian children aged 3-11 years, before (May) and after (December) the 2009 transmission season. To measure the effect of hemoglobin (Hb) type on antibody responses, we enrolled age-matched HbAA, HbAS and HbAC children. To quantify antibody recognition of iRBCs, we designed a high-throughput flow cytometry assay to rapidly test numerous plasma samples against multiple parasite strains. We evaluated antibody reactivity of each plasma sample to 3 laboratory-adapted parasite lines (FCR3, D10, PC26) and 4 short-term-cultured parasite isolates (2 Malian and 2 Cambodian). 97% of children recognized ≥1 parasite strain and the proportion of IgG responders increased significantly during the transmission season for most parasite strains. Both strain-specific and strain-transcending IgG responses were detected, and varied by age, Hb type and parasite strain. In addition, the breadth of IgG responses to parasite strains increased with age in HbAA, but not in HbAS or HbAC, children.Conclusions/SignificanceOur assay detects both strain-specific and strain-transcending IgG responses to iRBCs. The magnitude and breadth of these responses varied not only by age, but also by Hb type and parasite strain used. These findings indicate that studies of acquired humoral immunity should account for Hb type and test large numbers of diverse parasite strains.
Highlights
Plasmodium falciparum causes the most severe form of malaria, by some estimates placing more than 3 billion people at risk of disease and killing up to 1 million of them each year [1,2]
Increasing age and HbAS are associated with reduced malaria risk in Malian children We analyzed data from 176 Malian children aged 3-11 years who provided a plasma sample before and after the 2009 malaria transmission season
In another multivariate regression analysis accounting for age and Hb type, we found that IgG responses to multiple parasite strains were not associated with protection from malaria or delayed onset of malaria
Summary
Plasmodium falciparum causes the most severe form of malaria, by some estimates placing more than 3 billion people at risk of disease and killing up to 1 million of them each year [1,2]. As children experience multiple P. falciparum infections during childhood and adolescence, they develop successive stages of non-sterilizing immunity that protect them from severe and uncomplicated malaria, and eventually suppress their parasite densities [4,5]. This process produces an adult population with asymptomatic parasitemias that are often below the level of microscopic detection in thick blood films. 97% of children recognized ≥1 parasite strain and the proportion of IgG responders increased significantly during the transmission season for most parasite strains Both strain-specific and strain-transcending IgG responses were detected, and varied by age, Hb type and parasite strain. These findings indicate that studies of acquired humoral immunity should account for Hb type and test large numbers of diverse parasite strains
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