Recovery of adhesion to chondroitin-4-sulphate in Plasmodium falciparum varCSA disruption mutants by antigenically similar PfEMP1 variants

被引:27
作者
Andrews, KT
Pirrit, LA
Przyborski, JM
Sanchez, CP
Sterkers, Y
Ricken, S
Wickert, H
Lépolard, C
Avril, M
Scherf, A
Gysin, R
Lanzer, M [1 ]
机构
[1] Abt Parasitol, Inst Hyg, Heidelberg, Germany
[2] Inst Pasteur, Unite Biol Interact Hote Parasite, Paris, France
[3] Univ Mediterranee, Fac Med, Lab Parasitol Expt, Marseille, France
关键词
D O I
10.1046/j.1365-2958.2003.03595.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protection against maternal malaria has been associated with the acquisition of a specific antibody response that prevents adhesion of Plasmodium falciparum-infected erythrocytes to the glycosaminoglycan chondroitin-4-sulphate (CSA), which is present in the placental intervillous space. These antibodies are directed against variant forms of the P falciparum erythrocyte membrane protein 1 (PfEMP1) that mediate binding to CSA. We have generated insertional disruption mutants of the gene encoding the CSA-binding phenotype in the P. falciparum clone FCR3 (var(CSA)) to test the hypothesis that strategies targeting the parasite's determinant for this adhesive phenotype may prevent sequestration of infected erythrocytes in the placenta and hence the development of maternal malaria. The var(CSA)-disruption mutants were initially unable to adhere to CSA; however, they could recover the phenotype after repeated selection over CSA. We show that recovery of CSA binding is var(CSA) independent and mediated by the activation of a novel var variant. Importantly, the corresponding PfEMP1 protein reacts with a monoclonal antibody recognizing the DBL3gamma domain of the var(CSA) gene product, indicating that the DBL3gamma CSA-binding domains are conserved between these PfEMP1-binding variants. Our data support strategies exploring these conserved epitopes as vaccine candidates against maternal malaria.
引用
收藏
页码:655 / 669
页数:15
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