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Background: erythrocyte membrane protein 1 (PfEMP1) domains in plasma samples from 80 Burkinabe children (aged 0-60 months) collected before (pre-malaria season) and during peak malaria transmission. Methods: Using AlphaScreen, we measured antibody responses to 271 PfEMP1 (3D7) domains expressed via wheat germ cell-free synthesis. Results: Pre-season analysis showed that 96% of domains were IgG-reactive and IgG breadth increased with age, whereas 71% were IgM-reactive, but IgM breadth showed no age trend. IgG responses to 132 domains (49%) remained significantly associated with reduced risk of clinical malaria after false discovery rate (FDR) correction, including many non-adhesion domains. Five (5) IgM responses were nominally protective, but none remained significant after FDR correction. Fc-dependent opsonic phagocytosis assay using a subset of the top-ranked domains revealed that opsonic phagocytosis activity correlated with protection for only one antigen, suggesting that PfEMP1-specific antibodies may mediate protection through mechanisms beyond phagocytosis in children under 5 years old. Conclusions: This study provides the first comprehensive characterization of IgG and IgM responses to a large panel of PfEMP1 domains in young children, revealing broad antibody recognition and selective opsonic phagocytosis activity. Findings from the study deepen our understanding of early-life immunity to malaria and help identify PfEMP1 regions of interest for future vaccine development.
Dankyi et al. (Thu,) studied this question.