Recovery of adhesion to chondroitin-4-sulphate in Plasmodium falciparum var CSA disruption mutants by antigenically similar PfEMP1 variants
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 DBL3γ domain of the var CSA gene product, indicating that the DBL3γ CSA-binding domains are conserved between these PfEMP1-binding variants. Our data support strategies exploring these conserved epitopes as vaccine candidates against maternal malaria.
Document Type: Research Article
Affiliations: 1: Hygiene-Institut, Abteilung Parasitologie, Heidelberg, Germany. 2: Unite de Biologie des Interactions Hote-Parasite, Institut Pasteur, Paris, France. 3: Laboratoire de Parasitologie Experimentale, Faculte de Medecine, Universite de la Mediterranee, Marseille, France.
Publication date: 2003-08-01