Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1
Details
Publication Year 2022-02-17,Volume 90,Issue #2,Page e0043521
Journal Title
Infection and Immunity
Publication Type
Research article
Abstract
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a diverse family of multidomain proteins expressed on the surface of malaria-infected erythrocytes, is an important target of protective immunity against malaria. Our group recently studied transcription of the var genes encoding PfEMP1 in individuals from Papua, Indonesia, with severe or uncomplicated malaria. We cloned and expressed domains from 32 PfEMP1s, including 22 that were upregulated in severe malaria and 10 that were upregulated in uncomplicated malaria, using a wheat germ cell-free expression system. We used Luminex technology to measure IgG antibodies to these 32 domains and control proteins in 63 individuals (11 children). At presentation to hospital, levels of antibodies to PfEMP1 domains were either higher in uncomplicated malaria or were not significantly different between groups. Using principal component analysis, antibodies to 3 of 32 domains were highly discriminatory between groups. These included two domains upregulated in severe malaria, a DBLbeta13 domain and a CIDRalpha1.6 domain (which has been previously implicated in severe malaria pathogenesis), and a DBLdelta domain that was upregulated in uncomplicated malaria. Antibody to control non-PfEMP1 antigens did not differ with disease severity. Antibodies to PfEMP1 domains differ with malaria severity. Lack of antibodies to locally expressed PfEMP1 types, including both domains previously associated with severe malaria and newly identified targets, may in part explain malaria severity in Papuan adults.
Keywords
Adult; Antibodies, Protozoan; Child; Erythrocytes; Humans; Indonesia; *Malaria; *Malaria, Falciparum; Membrane Proteins/genetics; Plasmodium falciparum/genetics; Protozoan Proteins/genetics; PfEMP1; Plasmodium falciparum; humoral immunity; severe malaria
Department(s)
Laboratory Research
PubMed ID
34871039
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