strain-transcendent immune response to recombinant var2csa dbl5-ε domain block p. falciparum adhesion to placenta-derived bewo cells under flow conditionsstrain-transcendent免疫反应重组var2csa dbl5-ε域块恶性疟原虫粘附placenta-derived bewo细胞流条件下.pdfVIP

Strain-Transcendent Immune Response to Recombinant Var2CSA DBL5-e Domain Block P. falciparum Adhesion to Placenta-Derived BeWo Cells under Flow Conditions 1,2 ´ 3 ´ 1,2 ¨ 3 1,2 Pablo Fernandez , Stephane Petres , Salaheddine Mecheri , Jurg Gysin , Artur Scherf * ´ ˆ 1 Unite de Biologie des Interactions Hote-Parasite, Institut Pasteur, Paris, France, 2 CNRS URA2581, Paris, France, 3 Host Pathogen Interactions Unit, Institut Pasteur, Abymes, France Abstract Background: Pregnancy-associated malaria (PAM) is a serious consequence of the adhesion to the placental receptor chondroitin sulfate A (CSA) of Plasmodium falciparum-infected erythrocytes (PE) expressing the large cysteine-rich multi- domain protein var2CSA. Women become resistant to PAM, and develop strain-transcending immunity against CSA-binding parasites. The identification of var2CSA regions that could elicit broadly neutralizing and adhesion-blocking antibodies is a key step for the design of prophylactic vaccine strategies. Methodology: Escherichia coli expressed var2CSA DBL domains were refolded and purified prior to immunization of mice and a goat. Protein-G-purified antibodies were tested for their ability to block FCR3CSA-infected erythrocytes binding to placental (BeWo) and monkey brain endothelial (ScC2) cell lines using a flow cytoadhesion inhibition assay mimicking closely the physiological conditions present in the placenta at shear stress of 0.05 Pa. DBL5-e, DBL6-e and DBL5-6-e induced cross-reactive antibodies using Alum and Freund as adjuvants, which blocked cytoadhesion at values ranging between 40 to 96% at 0.5 mg IgG per ml. Imp