Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1
Issued Date
2022-02-01
Resource Type
ISSN
00199567
eISSN
10985522
Scopus ID
2-s2.0-85124850460
Pubmed ID
34871039
Journal Title
Infection and Immunity
Volume
90
Issue
2
Rights Holder(s)
SCOPUS
Bibliographic Citation
Infection and Immunity Vol.90 No.2 (2022)
Suggested Citation
Rambhatla J.S., Tonkin-Hill G.Q., Takashima E., Tsuboi T., Noviyanti R., Trianty L., Sebayang B.F., Lampah D.A., Marfurt J., Price R.N., Anstey N.M., Papenfuss A.T., Damelang T., Chung A.W., Duffy M.F., Rogerson S.J. Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1. Infection and Immunity Vol.90 No.2 (2022). doi:10.1128/iai.00435-21 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/85022
Title
Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1
Author's Affiliation
Faculty of Tropical Medicine, Mahidol University
School of Mathematics and Statistics
Bio21 Molecular Science and Biotechnology Institute
Eijkman Institute for Molecular Biology
Peter Maccallum Cancer Centre
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
Menzies School of Health Research
Nuffield Department of Medicine
Ehime University
Papuan Health and Community Development Foundation
School of Mathematics and Statistics
Bio21 Molecular Science and Biotechnology Institute
Eijkman Institute for Molecular Biology
Peter Maccallum Cancer Centre
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
Menzies School of Health Research
Nuffield Department of Medicine
Ehime University
Papuan Health and Community Development Foundation
Other Contributor(s)
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.