TY - JOUR
T1 - Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1
AU - Rambhatla, Janavi S.
AU - Tonkin-Hill, Gerry Q.
AU - Takashima, Eizo
AU - Tsuboi, Takafumi
AU - Noviyanti, Rintis
AU - Trianty, Leily
AU - Sebayang, Boni F.
AU - Lampah, Daniel A.
AU - Marfurt, Jutta
AU - Price, Ric N.
AU - Anstey, Nicholas M.
AU - Papenfuss, Anthony T.
AU - Damelang, Timon
AU - Chung, Amy W.
AU - Duffy, Michael F.
AU - Rogerson, Stephen J.
N1 - 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.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - Humoral immunity
KW - Indonesia
KW - PfEMP1
KW - Plasmodium falciparum
KW - Severe malaria
UR - http://www.scopus.com/inward/record.url?scp=85124850460&partnerID=8YFLogxK
U2 - 10.1128/iai.00435-21
DO - 10.1128/iai.00435-21
M3 - Article
C2 - 34871039
AN - SCOPUS:85124850460
VL - 90
SP - 1
EP - 14
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 2
M1 - e00435-21
ER -