1. Patterns of protective associations differ for antibodies to P. falciparum-infected erythrocytes and merozoites in immunity against malaria in children.
- Author
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Chan JA, Stanisic DI, Duffy MF, Robinson LJ, Lin E, Kazura JW, King CL, Siba PM, Fowkes FJ, Mueller I, and Beeson JG
- Subjects
- Adolescent, Age Factors, Antibodies, Protozoan pharmacology, Cell Line, Tumor, Child, Child, Preschool, Cohort Studies, Erythrocytes parasitology, Humans, Malaria, Falciparum parasitology, Malaria, Falciparum prevention & control, Monocytes immunology, Monocytes virology, Papua New Guinea, Phagocytosis drug effects, Phagocytosis immunology, Plasmodium falciparum genetics, Plasmodium falciparum pathogenicity, Protozoan Proteins genetics, Protozoan Proteins immunology, Virulence genetics, Virulence immunology, Antibodies, Protozoan immunology, Erythrocytes immunology, Immunity immunology, Malaria, Falciparum immunology, Merozoites immunology, Plasmodium falciparum immunology
- Abstract
Acquired antibodies play an important role in immunity to P. falciparum malaria and are typically directed towards surface antigens expressed by merozoites and infected erythrocytes (IEs). The importance of specific IE surface antigens as immune targets remains unclear. We evaluated antibodies and protective associations in two cohorts of children in Papua New Guinea. We used genetically-modified P. falciparum to evaluate the importance of PfEMP1 and a P. falciparum isolate with a virulent phenotype. Our findings suggested that PfEMP1 was the dominant target of antibodies to the IE surface, including functional antibodies that promoted opsonic phagocytosis by monocytes. Antibodies were associated with increasing age and concurrent parasitemia, and were higher among children exposed to a higher force-of-infection as determined using molecular detection. Antibodies to IE surface antigens were consistently associated with reduced risk of malaria in both younger and older children. However, protective associations for antibodies to merozoite surface antigens were only observed in older children. This suggests that antibodies to IE surface antigens, particularly PfEMP1, play an earlier role in acquired immunity to malaria, whereas greater exposure is required for protective antibodies to merozoite antigens. These findings have implications for vaccine design and serosurveillance of malaria transmission and immunity., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
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