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

被引:46
作者
Chattopadhyay, R
Rathore, D
Fujioka, H
Kumar, S
de la Vega, P
Haynes, D
Moch, K
Fryauff, D
Wang, RB
Carucci, DJ
Hoffman, SL
机构
[1] USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA
[2] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA
[3] Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA
关键词
D O I
10.1074/jbc.M300865200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:25977 / 25981
页数:5
相关论文
共 37 条
[11]   Genome sequence of the human malaria parasite Plasmodium falciparum [J].
Gardner, MJ ;
Hall, N ;
Fung, E ;
White, O ;
Berriman, M ;
Hyman, RW ;
Carlton, JM ;
Pain, A ;
Nelson, KE ;
Bowman, S ;
Paulsen, IT ;
James, K ;
Eisen, JA ;
Rutherford, K ;
Salzberg, SL ;
Craig, A ;
Kyes, S ;
Chan, MS ;
Nene, V ;
Shallom, SJ ;
Suh, B ;
Peterson, J ;
Angiuoli, S ;
Pertea, M ;
Allen, J ;
Selengut, J ;
Haft, D ;
Mather, MW ;
Vaidya, AB ;
Martin, DMA ;
Fairlamb, AH ;
Fraunholz, MJ ;
Roos, DS ;
Ralph, SA ;
McFadden, GI ;
Cummings, LM ;
Subramanian, GM ;
Mungall, C ;
Venter, JC ;
Carucci, DJ ;
Hoffman, SL ;
Newbold, C ;
Davis, RW ;
Fraser, CM ;
Barrell, B .
NATURE, 2002, 419 (6906) :498-511
[12]   Antibodies that inhibit malaria merozoite surface protein-1 processing and erythrocyte invasion are blocked by naturally acquired human antibodies [J].
Guevara-Patino, JA ;
Holder, AA ;
McBride, JS ;
Blackman, MJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (10) :1689-1699
[13]   PROTEIN FAMILY CLASSIFICATION BASED ON SEARCHING A DATABASE OF BLOCKS [J].
HENIKOFF, S ;
HENIKOFF, JG .
GENOMICS, 1994, 19 (01) :97-107
[14]   SAFETY AND IMMUNOGENICITY IN MAN OF A SYNTHETIC PEPTIDE MALARIA VACCINE AGAINST PLASMODIUM-FALCIPARUM SPOROZOITES [J].
HERRINGTON, DA ;
CLYDE, DF ;
LOSONSKY, G ;
CORTESIA, M ;
MURPHY, JR ;
DAVIS, J ;
BAQAR, S ;
FELIX, AM ;
HEIMER, EP ;
GILLESSEN, D ;
NARDIN, E ;
NUSSENZWEIG, RS ;
NUSSENZWEIG, V ;
HOLLINGDALE, MR ;
LEVINE, MM .
NATURE, 1987, 328 (6127) :257-259
[15]   Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites [J].
Hoffman, SL ;
Goh, LML ;
Luke, TC ;
Schneider, I ;
Le, TP ;
Doolan, DL ;
Sacci, J ;
de la Vega, P ;
Dowler, M ;
Paul, C ;
Gordon, DM ;
Stoute, JA ;
Church, LWP ;
Sedegah, M ;
Heppner, DG ;
Ballou, WR ;
Richie, TL .
JOURNAL OF INFECTIOUS DISEASES, 2002, 185 (08) :1155-1164
[16]   SAFETY, IMMUNOGENICITY, AND EFFICACY OF A MALARIA SPOROZOITE VACCINE ADMINISTERED WITH MONOPHOSPHORYL LIPID A, CELL-WALL SKELETON OF MYCOBACTERIA, AND SQUALANE AS ADJUVANT [J].
HOFFMAN, SL ;
EDELMAN, R ;
BRYAN, JP ;
SCHNEIDER, I ;
DAVIS, J ;
SEDEGAH, M ;
GORDON, D ;
CHURCH, P ;
GROSS, M ;
SILVERMAN, C ;
HOLLINGDALE, M ;
CLYDE, D ;
SZTEIN, M ;
LOSONSKY, G ;
PAPARELLO, S ;
JONES, TR .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1994, 51 (05) :603-612
[17]   Plasmodium, human and Anopheles genomics and malaria [J].
Hoffman, SL ;
Subramanian, GM ;
Collins, FH ;
Venter, JC .
NATURE, 2002, 415 (6872) :702-709
[18]   Cell biology: Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes [J].
Hutter, H ;
Vogel, BE ;
Plenefisch, JD ;
Norris, CR ;
Proenca, RB ;
Spieth, J ;
Guo, CB ;
Mastwal, S ;
Zhu, XP ;
Scheel, J ;
Hedgecock, EM .
SCIENCE, 2000, 287 (5455) :989-994
[19]   Exploring the transcriptome of the malaria sporozoite stage [J].
Kappe, SHI ;
Gardner, MJ ;
Brown, SM ;
Ross, J ;
Matuschewski, K ;
Ribeiro, JM ;
Adams, JH ;
Quackenbush, J ;
Cho, J ;
Carucci, DJ ;
Hoffman, SL ;
Nussenzweig, V .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (17) :9895-9900
[20]   THE STRUCTURE OF HUMAN THROMBOSPONDIN, AN ADHESIVE GLYCOPROTEIN WITH MULTIPLE CALCIUM-BINDING SITES AND HOMOLOGIES WITH SEVERAL DIFFERENT PROTEINS [J].
LAWLER, J ;
HYNES, RO .
JOURNAL OF CELL BIOLOGY, 1986, 103 (05) :1635-1648