Anti-plasmodium compositions and methods of use

Abstract

Compositions that inhibit the binding of Plasmodium falciparum to erythrocytes include a family of erythrocyte binding proteins (EBPs). The EBPs are paralogues of the P. falciparum binding protein EBA- 175 . The present invention includes peptides of the paralogues that prevent the binding of P. falciparum . Antibodies specific for each paralogue that also prevent the binding of P. falciparum are also included. Methods of the invention utilize the paralogues, antibodies thereof and peptide compositions for the diagnosis, prevention, and treatment of P. falciparum diseases such as malaria, as well as methods for the detection of P. falciparum in biological samples and culture media.

What is claimed is:  
     
         1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an isolated polypeptide comprising a paralogue of EBA-175 polypeptide sequence.  
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the paralogue of EBA-175 polypeptide sequence is encoded by the sequence of SEQ ID NO:1.  
     
     
         3 . The pharmaceutical composition of  claim 1 , further comprising an isolated sialic acid binding protein (SABP) binding domain polypeptide in an amount sufficient to induce a protective immune response to  Plasmodium falciparum  merozoites in a mammal.  
     
     
         4 . An isolated polypeptide comprising a paralogue of EBA-175 polypeptide sequence.  
     
     
         5 . The isolated polypeptide of  claim 4 , wherein the paralogue of EBA-175 polypeptide sequence is encoded by the sequence of SEQ ID NO:1.  
     
     
         6 . An isolated nucleic acid sequence comprising a paralogue of EBA-175 nucleic acid sequence.  
     
     
         7 . The isolated nucleic acid sequence of  claim 6 , wherein the paralogue of EBA-175 nucleic acid sequence comprises the sequence of SEQ ID NO:1.  
     
     
         8 . A vector comprising a paralogue of EBA-175 nucleic acid sequence.  
     
     
         9 . The vector of  claim 8 , wherein the paralogue of EBA-175 nucleic acid sequence comprises the sequence of SEQ ID NO:1.  
     
     
         10 . A recombinant host cell comprising a paralogue of EBA-175 nucleic acid sequence.  
     
     
         11 . The recombinant host cell of  claim 10 , wherein the paralogue of EBA-175 nucleic acid sequence comprises the sequence of SEQ ID NO:1.  
     
     
         12 . A recombinant host cell comprising the vector of  claim 8 .  
     
     
         13 . A method for an immune response to  Plasmodium falciparum  merozoites in a patient, the method comprising administration to the patient of an immunologically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an isolated polypeptide comprising a paralogue of EBA-175 polypeptide sequence.  
     
     
         14 . The method of  claim 13 , wherein the paralogue of EBA-175 polypeptide sequence is encoded by the sequence of SEQ ID NO:1.  
     
     
         15 . The method of  claim 14 , further comprising administration to the patient of an immunologically effective amount of an isolated SABP binding domain polypeptide.  
     
     
         16 . A recombinant method for making a paralogue of EBA-175 polypeptide, comprising: 
 expressing the vector of  claim 8  in a host cell; and    isolating the paralogue of EBA-175 polypeptide from said host cell.    
     
     
         17 . An isolated antibody, wherein the antibody binds a 5′ cysteine rich region of an EBA-175 protein paralogue from a Plasmodium species.  
     
     
         18 . The isolated antibody of  claim 17 , wherein the 5′ cysteine rich region is a region II.  
     
     
         19 . The isolated antibody of  claim 18 , wherein the 5′ cysteine rich region is a region II/F2.  
     
     
         20 . The isolated antibody of  claim 17 , wherein the antibody inhibits binding of an EBA-175 protein to a red blood cell.