Gangnard S., Tuikue Ndam Nicaise, Gnidehou Sédami, Quiviger Michael, Juillerat A., Faure G., Baron B., Viwami Firmine, Deloron Philippe, Bentley G. A. (2010). Functional and immunological characterization of the var2CSA-DBL5 epsilon domain of a placental Plasmodium falciparum isolate. Molecular and Biochemical Parasitology, 173 (2), p. 115-122. ISSN 0166-6851.
Titre du document
Functional and immunological characterization of the var2CSA-DBL5 epsilon domain of a placental Plasmodium falciparum isolate
Gangnard S., Tuikue Ndam Nicaise, Gnidehou Sédami, Quiviger Michael, Juillerat A., Faure G., Baron B., Viwami Firmine, Deloron Philippe, Bentley G. A.
Source
Molecular and Biochemical Parasitology, 2010,
173 (2), p. 115-122 ISSN 0166-6851
Pregnancy-associated malaria (PAM) arises from sequestration of Plasmodium falciparum-parasitized erythrocytes (PE) in the placenta, leading to chronic symptoms in the expectant mother and serious consequences for fetal development. Placental sequestration has been linked to binding of chondroitin sulphate A (CSA) by the var2CSA variant of PfEMP1 expressed on the PE surface, and a substantial body of evidence shows that the immune response to var2CSA gives an effective protection against PAM. We have expressed the var2CSA-DBL5 epsilon domain, derived from a placental isolate from Senegal, as soluble product in Escherichia coil and have shown using different criteria that the recombinant protein is obtained with the native conformation. Using surface plasmon resonance techniques, we have examined binding of DBL5 epsilon to placental chondroitin sulphate proteoglyan and CSA; however, the recombinant protein also binds to other sulphated oligosaccharides, with higher affinity in some cases, indicating that the single domain lacks the specificity for CSA shown by the complete extra-cellular region of var2CSA and placental parasites. Recombinant DBL5 epsilon was specifically recognized by sera from malaria-exposed Senegalese women in a parity-dependent manner but by sera not from children or males from the same endemic region. Conversely, DBL5 epsilon induced antibodies in mice that recognized placental isolates from Benin but not isolates from children. The presence of universal epitopes thus supports DBL5 epsilon as an interesting component of var2CSA to be considered for vaccine development.
