PfSPATR, a Plasmodium falciparum protein containing an altered thrombospondin type I repeat domain is expressed at several stages of the parasite life cycle and is the target of inhibitory antibodies.
The annotated sequence of chromosome 2 of Plasmodium falciparum was examined for genes encoding proteins that may be of interest for vaccine development. We describe here the characterization of a protein with an altered thrombospondin Type I repeat domain (PfSPATR) that is expressed in the sporozoite, asexual, and sexual erythrocytic stages of the parasite life cycle. Immunoelectron microscopy indicated that this protein was expressed on the surface of the sporozoites and around the rhoptries in the asexual erythrocytic stage. An Escherichia coli-produced recombinant form of the protein bound to HepG2 cells in a dose-dependent manner and antibodies raised against this protein blocked the invasion of sporozoites into a transformed hepatoma cell line. Sera from Ghanaian adults and from a volunteer who had been immunized with radiation-attenuated P. falciparum sporozoites specifically recognized the expression of this protein on transfected COS-7 cells. These data support the evaluation of this protein as a vaccine candidate.
Chattopadhyay
Rana
R
Malaria Program, Naval Medical Research Center, Silver Spring, Maryland 20910-7500, USA.
Rathore
Dharmendar
D
Fujioka
Hishasi
H
Kumar
Sanjai
S
de la Vega
Patricia
P
Haynes
David
D
Moch
Kathleen
K
Fryauff
David
D
Wang
Ruobing
R
Carucci
Daniel J
DJ
Hoffman
Stephen L
SL
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008288:Malaria / Q000097:blood; D051379:Mice; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000737:chemistry*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019699:Thrombospondins / Q000737:chemistry*; D014158:Transcription, Genetic; D014162:Transfection
D018076:DNA, Complementary; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C476250:SPATR protein, Plasmodium falciparum; D019699:Thrombospondins