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Prepublished online as a Blood First Edition Paper on May 17, 2002; DOI 10.1182/blood-2002-01-0315. This Article Full Text (PDF) All Versions of this Article: 2002-01-0315v1 100/4/1478    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lekana Douki, J. B. Articles by Gysin, J. Search for Related Content PubMed PubMed Citation Articles by Lekana Douki, J. B. Articles by Gysin, J. Social Bookmarking                   What's this? Submitted February 21, 2002 Accepted April 4, 2002 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 Jean Bernard Lekana Douki, Boubacar Traore, Fabio T Costa, Thierry Fusai, Bruno Pouvelle, Yvon Sterkers, Artur Scherf, and Jurg Gysin* Unite de Parasitologie Experimentale URA IPP/UNIV-MED/IMTSSA EA3282, IFR 48, Universite de la Mediterranee, Institut Pasteur, Marseille, France Parasitologie EA3282, IMTSSA/UNIV-MED, MARSEILLE, France BHIP, Institut Pasteur, Paris, France * Corresponding author; email: gysin{at}medecine.univ-mrs.fr. P. falciparum parasites express variant adhesion molecules on the surface of infected erythrocytes (IE), 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 DBL-3 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 CHO cells before injecting P. falciparum-infected erythrocytes or transfected CHO cells expressing the CSA-binding domain (DBL-3) 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 geographical areas and to placental isolates from Central Africa. The cross-reactive mabs are directed against the DBL-3CSA , demonstrating that this domain, which mediates CSA binding is able to induce a pan-reactive immune response. This work is an important step towards the development of a DBL-3-based vaccine that could protect pregnant women from pathogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Mo, H. C. Lee, M. Kotaka, M. Niang, X. Gao, J. K. Iyer, J. Lescar, and P. Preiser The C-Terminal Segment of the Cysteine-Rich Interdomain of Plasmodium falciparum Erythrocyte Membrane Protein 1 Determines CD36 Binding and Elicits Antibodies That Inhibit Adhesion of Parasite-Infected Erythrocytes Infect. Immun., May 1, 2008; 76(5): 1837 - 1847. [Abstract] [Full Text] [PDF] A. A. ADEGNIKA, J. J. VERWEIJ, S. 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