Abstract

Naturally acquired humoral immunity to the malarial parasite Plasmodium falciparum can protect against disease, although the precise mechanisms remain unclear. Although antibody levels can be measured by ELISA, few studies have investigated functional antibody assays in relation to clinical outcomes. In this study we applied a recently developed functional assay of antibody-mediated opsonisation of merozoites, to plasma samples from a longitudinal cohort study conducted in a malaria endemic region of Papua New Guinea (PNG). Phagocytic activity was quantified by flow cytometry using a standardized and high-throughput protocol, and was subsequently evaluated for association with protection from clinical malaria and high-density parasitemia. Opsonising antibody responses were found to: i) increase with age, ii) be enhanced by concurrent infection, and iii) correlate with protection from clinical episodes and high-density parasitemia. Stronger protective associations were observed in individuals with no detectable parasitemia at baseline. This study presents the first evidence for merozoite phagocytosis as a correlate of acquired immunity and clinical protection against P. falciparum malaria.

Highlights

  • Malaria is caused by the protozoan parasites Plasmodium spp., of which Plasmodium falciparum is responsible for most of the mortality and morbidity associated with the disease worldwide

  • When this assay was applied to plasma samples from 198 Papua New Guinean (PNG) children, the percentage of THP-1 cells that had phagocytosed merozoites ranged from 5–79%

  • Merozoite invasion has been proposed to occur within seconds following schizont rupture [32], casting doubt on the ability of merozoite phagocytosis to be an effective anti-parasite mechanism

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Summary

Introduction

Malaria is caused by the protozoan parasites Plasmodium spp., of which Plasmodium falciparum is responsible for most of the mortality and morbidity associated with the disease worldwide. Individuals living in malaria-endemic areas can develop both humoral and cell mediated immunity over time and with exposure (reviewed in [4]). This immunity is non-sterilising, it results in reduced parasite densities and protection from lifethreatening clinical disease. Transfer of c-globulin from immune African adults to non-immune children alleviated severe disease [5,6], which demonstrates the importance of antibodies for clinical protection against P. falciparum malaria

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