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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
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
Blood, Volume 100, No. 4, Year 2002
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Description
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)-γ3 domain of P falciparum erythrocyte membrane protein 1 (PfEMP1CSA). 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-γ3) of the FCR3 varCSA 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 (mIECSA) but not of other adhesive phenotypes. Surprisingly, 70.8% of the 43 mAbs analyzed in this work were IgM. All mAbs immunoprecipitated PfEMP1CSA from extracts of 125I surface-labeled IECSA. 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-γ3CSA, 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-γ3-based vaccine that could protect pregnant women from pathogenesis. © 2002 by The American Society of Hematology.
Authors & Co-Authors
Traoré, Boubacar M.
France, Marseille
Aix Marseille Université
France, Paris
Institut Pasteur, Paris
Costa, Fábio Trindade Maranhão Trindade Maranhão
France, Marseille
Aix Marseille Université
France, Paris
Institut Pasteur, Paris
Fusaï, Thierry
France, Marseille
Aix Marseille Université
France, Paris
Institut Pasteur, Paris
Pouvelle, Bruno
France, Marseille
Aix Marseille Université
France, Paris
Institut Pasteur, Paris
Sterkers, Yvon
France, Marseille
Aix Marseille Université
France, Paris
Institut Pasteur, Paris
Scherf, Artur
France, Marseille
Aix Marseille Université
France, Paris
Institut Pasteur, Paris
Gysin, Jürg
France, Marseille
Aix Marseille Université
France, Paris
Institut Pasteur, Paris
Statistics
Citations: 55
Authors: 7
Affiliations: 2
Identifiers
Doi:
10.1182/blood-2002-01-0315
ISSN:
00064971
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Locations
Multi-countries
Participants Gender
Female