Sequestration of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A, a receptor for maternal malaria: monoclonal antibodies against the native parasite ligand reveal pan-reactive epitopes in placental isolates.
نویسندگان
چکیده
Plasmodium falciparum parasites express variant adhesion molecules on the surface of infected erythrocytes (IEs), which act as targets for natural protection. Recently it was shown that IE sequestration in the placenta is mediated by binding to chondroitin sulfate A via the duffy binding-like (DBL)-gamma 3 domain of P falciparum erythrocyte membrane protein 1 (PfEMP1(CSA)). Conventional immunization procedures rarely result in the successful production of monoclonal antibodies (mAbs) against such conformational vaccine candidates. Here, we show that this difficulty can be overcome by rendering Balb/c mice B cells tolerant to the surface of human erythrocytes or Chinese hamster ovary (CHO) cells before injecting P falciparum IEs or transfected CHO cells expressing the chondroitin sulfate A (CSA)-binding domain (DBL-gamma 3) of the FCR3 var(CSA) gene. We fused spleen cells with P3U1 cells and obtained between 20% and 60% mAbs that specifically label the surface of mature infected erythrocytes of the CSA phenotype (mIE(CSA)) but not of other adhesive phenotypes. Surprisingly, 70.8% of the 43 mAbs analyzed in this work were IgM. All mAbs immunoprecipitated PfEMP1(CSA) from extracts of (125)I surface-labeled IE(CSA). Several mAbs bound efficiently to the surface of CSA-binding parasites from different geographic areas and to placental isolates from West Africa. The cross-reactive mAbs are directed against the DBL-gamma 3(CSA), demonstrating that this domain, which mediates CSA binding, is able to induce a pan-reactive immune response. This work is an important step toward the development of a DBL-gamma 3-based vaccine that could protect pregnant women from pathogenesis. )
منابع مشابه
Sequestration of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A, a receptor for maternal malaria: monoclonal antibodies against the native parasite ligand reveal pan-reactive epitopes in placental isolates Running head: Pan-reactive anti-PfEMP1var monoclonal antibodies
متن کامل
The NTS-DBL2X region of VAR2CSA induces cross-reactive antibodies that inhibit adhesion of several Plasmodium falciparum isolates to chondroitin sulfate A.
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Sequestration of Plasmodium falciparum-infected erythrocytes in the placenta is implicated in pathological outcomes of pregnancy-associated malaria (PAM). P. falciparum isolates that sequester in the placenta primarily bind chondroitin sulfate A (CSA). Following exposure to malaria during pregnancy, women in areas of endemicity develop immunity, and so multigravid women are less susceptible to ...
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ورودعنوان ژورنال:
- Blood
دوره 100 4 شماره
صفحات -
تاریخ انتشار 2002