Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1

Janavi S. Rambhatla, Gerry Q. Tonkin-Hill, Eizo Takashima, Takafumi Tsuboi, Rintis Noviyanti, Leily Trianty, Boni F. Sebayang, Daniel A. Lampah, Jutta Marfurt, Ric N. Price, Nicholas M. Anstey, Anthony T. Papenfuss, Timon Damelang, Amy W. Chung, Michael F. Duffy, Stephen J. Rogerson

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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 DBLb13 domain and a CIDRa1.6 domain (which has been previously implicated in severe malaria pathogenesis), and a DBLd 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.

Original languageEnglish
Article numbere00435-21
Pages (from-to)1-14
Number of pages14
JournalInfection and Immunity
Volume90
Issue number2
DOIs
Publication statusPublished - 1 Feb 2022

Bibliographical note

Funding Information:
Sample collection and analysis were supported by the National Health and Medical Research Council (project grant to M.F.D. [GNT1007954]; program grants to N.M.A., R.N.P. [GNT1037304], and S.J.R. [GNT1092789]; and fellowships to N.M.A. [GNT1135820], A.T.P. [GNT1116955], and A.W.C. [GNT1140509]). Protein expression was partially supported by a JSPS KAKENHI grant, Japan, to E.T. (JP21H02724). R.N.P. is a Wellcome Trust Senior Fellow in Clinical Science (200909). J.S.R. was supported by a Melbourne International Research Scholarship and Melbourne International Fee Remission Scholarship from the University of Melbourne.

Publisher Copyright:
© 2022 American Society for Microbiology.

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