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J Infect Dis. 2018 Oct 26. doi: 10.1093/infdis/jiy580. [Epub ahead of print]

Antibody Targets on the Surface of Plasmodium falciparum-Infected Erythrocytes That Are Associated With Immunity to Severe Malaria in Young Children.

Author information

1
Burnet Institute for Medical Research and Public Health, Melbourne.
2
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville.
3
Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne.
4
Department of Medicine, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia.
5
Center for Infectious Diseases Research, Seattle, Washington.
6
Papua New Guinea Institute of Medical Research, Madang.
7
University of Western Australia, Perth.
8
Walter and Eliza Hall Institute of Medical Research, Parkville.
9
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
10
Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia.
11
Department of Microbiology, Monash University, Melbourne, Victoria, Australia.

Abstract

Background:

Sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the microvasculature contributes to pathogenesis of severe malaria in children. This mechanism is mediated by antigens expressed on the IE surface. However, knowledge of specific targets and functions of antibodies to IE surface antigens that protect against severe malaria is limited.

Methods:

Antibodies to IE surface antigens were examined in a case-control study of young children in Papua New Guinea presenting with severe or uncomplicated malaria (n = 448), using isolates with a virulent phenotype associated with severe malaria, and functional opsonic phagocytosis assays. We used genetically modified isolates and recombinant P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains to quantify PfEMP1 as a target of antibodies associated with disease severity.

Results:

Antibodies to the IE surface and recombinant PfEMP1 domains were significantly higher in uncomplicated vs severe malaria and were boosted following infection. The use of genetically modified P. falciparum revealed that PfEMP1 was a major target of antibodies and that PfEMP1-specific antibodies were associated with reduced odds of severe malaria. Furthermore, antibodies promoting the opsonic phagocytosis of IEs by monocytes were lower in those with severe malaria.

Conclusions:

Findings suggest that PfEMP1 is a dominant target of antibodies associated with reduced risk of severe malaria, and function in part by promoting opsonic phagocytosis.

PMID:
30365004
DOI:
10.1093/infdis/jiy580

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