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Eur J Immunol. 2017 Dec;47(12):2124-2136. doi: 10.1002/eji.201747032. Epub 2017 Sep 13.

Patterns of protective associations differ for antibodies to P. falciparum-infected erythrocytes and merozoites in immunity against malaria in children.

Author information

1
Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia.
2
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
3
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
4
Institute for Glycomics, Griffith University, Southport, Queensland, Australia.
5
Department of Medicine and Melbourne School of Public Health, University of Melbourne, Parkville, Victoria, Australia.
6
Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
7
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA.
8
Melbourne School of Public Health, University of Melbourne, Parkville, Victoria, Australia.
9
Department of Epidemiology and Preventive Medicine and Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia.
10
Department of Microbiology, Monash University, Melbourne, Victoria, Australia.

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.

KEYWORDS:

Antibodies; Immunity; Malaria; PfEMP1; Plasmodium falciparum

PMID:
28833064
PMCID:
PMC5893221
[Available on 2018-12-01]
DOI:
10.1002/eji.201747032
[Indexed for MEDLINE]

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