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J. Biol. Chem., Vol. 278, Issue 28, 25977-25981, July 11, 2003

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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^*

Rana Chattopadhyay, Dharmendar Rathore , Hishasi Fujioka , Sanjai Kumar, Patricia de la Vega, David Haynes, Kathleen Moch, David Fryauff, Ruobing Wang, Daniel J. Carucci and Stephen L. Hoffman ¶

From the Malaria Program, Naval Medical Research Center, Silver Spring, Maryland 20910-7500, Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0425, and the Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106

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.

Received for publication, January 27, 2003 , and in revised form, April 11, 2003.

^* This work was supported by Naval Medical Research and Development Command Work Unit 6000.RAD1.F.A0309. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Sanaria, 308 Argosy Drive, Gaithersburg, MD 20878. Tel.: 240-299-3178; Fax: 301-990-6370; E-mail: SLHoffman{at}sanaria.com.

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