Functional and immunological characterization of a duffy binding-like- gamma domain from Plasmodium falciparum erythrocyte membrane protein-1 expressed by a placental isolate.
A recombinant Duffy binding-like (DBL)- gamma domain from a previously identified placental isolate, 732, was expressed by use of the baculovirus/insect cell system and was purified in milligram quantities. The recombinant protein binds specifically to chondroitin sulfate A (CSA) and inhibits CSA binding by placental infected erythrocytes (IEs). Polyclonal antibodies raised against the domain recognized the surfaces of live IEs from CSA-adherent clinical placental isolates. These antibodies also abrogated the in vitro binding of IEs to CSA. The 732 DBL-3 gamma domain was specifically recognized by plasma from pregnant women but not by plasma from control subjects. In addition, the protein was, comparatively, significantly more reactive with plasma from women with infected placentas, strongly suggesting that the 732 DBL-3 gamma domain carries preferentially IE-expressed immunogenic epitopes. High levels of plasma antibodies to the recombinant domain were associated with reduced placental parasite density. This is the first report of a recombinant DBL- gamma domain derived from a placental isolate that shows CSA-binding properties.
Chia
Yu-Shan
YS
Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Badaut
Cyril
C
Tuikue Ndam
Nicaise G
NG
Khattab
Ayman
A
Igonet
Sebastien
S
Fievet
Nadine
N
Bentley
Graham A
GA
Deloron
Philippe
P
Klinkert
Mo-Quen
MQ
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D016466:CHO Cells; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism*; D006224:Cricetinae; D004375:Duffy Blood-Group System / Q000378:metabolism*; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology; D008297:Male; D008969:Molecular Sequence Data; D010920:Placenta / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000469:parasitology; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018411:Spodoptera
D000913:Antibodies, Protozoan; D004375:Duffy Blood-Group System; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D002809:Chondroitin Sulfates