Immunization with Recombinant Duffy Binding–Like–γ3 Induces Pan‐Reactive and Adhesion‐Blocking Antibodies against Placental Chondroitin Sulfate A–Binding Plasmodium falciparum Parasites
In: Journal of Infectious Diseases Journal of Infectious Diseases, 2003, 188 (1), pp.153-164. ⟨10.1086/375800⟩ Journal of Infectious Diseases, Oxford University Press (OUP), 2003, 188 (1), pp.153-164. ⟨10.1086/375800⟩; (2003-07-01)
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Zugriff:
International audience; Maternal malaria is associated with the sequestration, in the placenta, of Plasmodium falciparum-infected erythrocytes onto chondroitin sulfate A (CSA), via the duffy binding-like (DBL)-gamma3 domain of the P. falciparum erythrocyte membrane protein 1 (PfEMP1(CSA)) (DBL-gamma3(CSA)). The production of antibodies against CSA-binding infected erythrocytes (IEs(CSA)) is correlated with resistance to maternal malaria in multiparous women. We produced recombinant DBL-gamma3(CSA) (rDBL-gamma3(CSA)) in insect cells, corresponding to 2 variant DBL-gamma3(CSA) subtypes that mediate binding to CSA in laboratory lines and placental isolates. Both recombinant cysteine-rich DBL-gamma3(CSA) domains blocked IEs(CSA) binding to CSA. Immunization of mice, with the rDBL-gamma3(CSA)-FCR3 and rDBL-gamma3(CSA)-3D7 domains, resulted in the generation of antibodies recognizing homologous and heterologous rDBL-gamma3(CSA), a finding indicating conserved epitopes inducing a pan-reactive immune response. Mouse monoclonal antibodies (MAbs) against both recombinant proteins were pan-reactive with various IEs(CSA). One MAb efficiently inhibited and reversed IE(CSA) cytoadhesion to endothelial cells in vitro. Thus, DBL-gamma3(CSA) is the target of inhibitory and pan-reactive antibodies. Saimiri sciureus monkeys immunized with FCR3-rDBL-gamma3(CSA) developed pan-reactive and inhibitory antibodies, a finding suggesting that the development of a vaccine to prevent maternal malaria is feasible.
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Immunization with Recombinant Duffy Binding–Like–γ3 Induces Pan‐Reactive and Adhesion‐Blocking Antibodies against Placental Chondroitin Sulfate A–Binding Plasmodium falciparum Parasites
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Autor/in / Beteiligte Person: | Scherf, Artur ; Gysin, Jürg ; Costa, Fabio T. M. ; Petres, Stéphane ; Parzy, Daniel ; Jean-Bernard Lekana Douki ; Traore, Boubacar ; Torrentino, Marylin ; Fusaï, Thierry ; Sterkers, Yvon ; Expérimentale, Parasitologie ; Université de la Méditerranée - Aix-Marseille 2-Biologie des Interactions Hôte-Parasite ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) ; Aix-Marseille Université - Faculté de médecine (AMU MED) ; Aix Marseille Université (AMU) ; Biologie des Interactions Hôte-Parasite ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) ; Département de Biologie structurale et Chimie - Department of Structural Biology and Chemistry ; Institut Pasteur [Paris] (IP) ; Program PAL+ 2000 of the Ministère de l'Education Nationale de la Recherche et de la Technologie (DGA/PEA 980814) ; European Union for Research and Technical Development (contract IC18-CT98-0362 and QLK2-CT2000-00109 ; fellowships to F.T.M.C., B.T., and Y.S.) ; CNPq-Brazil (fellowship 200076/95-7 to F.T.M.C.) ; Bourses et Stages Gabon-BGE (grants 1998-753 and FRM-FDT 20010920048/1 to J.B.L.D.). ; We thank C. Lépolard for technical assistance with hybridoma fusions and parasite cultures. ; Unité de parasitologie expérimentale ; Université de la Méditerranée - Aix-Marseille 2 ; Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) ; Institut Pasteur [Paris] ; Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) |
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Quelle: | Journal of Infectious Diseases Journal of Infectious Diseases, 2003, 188 (1), pp.153-164. ⟨10.1086/375800⟩ Journal of Infectious Diseases, Oxford University Press (OUP), 2003, 188 (1), pp.153-164. ⟨10.1086/375800⟩; (2003-07-01) |
Veröffentlichung: | HAL CCSD, 2003 |
Medientyp: | unknown |
ISSN: | 0022-1899 (print) ; 1537-6613 (print) |
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