Toxoplasma gondii apical membrane antigen-1

Abstract

The invention provides polypeptide fragments derived from TgAMA-1, nucleic acids that encode the polypeptide fragments, and TgAMA-binding polypeptides such as antibodies. Methods for using the polypeptide and nucleic acid molecules to produce vaccines are also provided. In addition the invention provides methods involving use of the polypeptides, nucleic acids, and binding polypeptides, such as antibodies, for the prevention and treatment of Toxoplasmosis.

1 . An isolated TgAMA-1 polypeptide molecule comprising an antigenic fragment of the polypeptide sequence set forth as amino acids SEQ ID NO:1.  
     
     
         2 . A fusion protein comprising the antigenic polypeptide of  claim 1 .  
     
     
         3 . An isolated TgAMA-1 nucleic acid molecule selected from the group consisting of: 
 (a) a fragment of the nucleotide sequence set forth as nucleotides 1-2507 of SEQ ID NO:2 between 12 and 2506 nucleotides in length, and    (b) complements of (a),    wherein the fragment encodes the isolated polypeptide of  claim 1 .    
     
     
         4 . An expression vector comprising the isolated nucleic acid sequence of  claim 3  operably linked to a promoter.  
     
     
         5 . An expression vector comprising an isolated nucleic acid molecule of SEQ ID NO:2. operably linked to a promoter.  
     
     
         6 . A host cell transformed or transfected with the expression vector of  claim 4 .  
     
     
         7 . A transgenic non-human animal comprising the expression vector of  claim 4 .  
     
     
         8 . The transgenic non-human animal of  claim 7 , wherein the animal expresses a variable level of TgAMA-1.  
     
     
         9 . The transgenic non-human animal of  claim 7 , wherein the animal expresses an antigenic fragment of SEQ ID NO:1.  
     
     
         10 . A composition comprising the isolated TgAMA-1 polypeptide of  claim 1  and an adjuvant.  
     
     
         11 . A composition comprising TgAMA-1 or a functionally active variant thereof, and an adjuvant.  
     
     
         12 . A method for immunizing a subject comprising 
 administering to the subject an effective amount for immunizing the subject of a composition of  claim 10 .    
     
     
         13 . The method of  claim 12 , wherein the subject is at risk of infection from  Toxoplasma gondii.    
     
     
         14 . A TgAMA-1 binding polypeptide that selectively binds to the isolated TgAMA-1 polypeptide of  claim 1 .  
     
     
         15 . The TgAMA-1 binding polypeptide of  claim 14 , wherein the binding polypeptide is an antibody or antigen-binding fragment of an antibody.  
     
     
         16 . The TgAMA-1 binding polypeptide of  claim 15 , wherein the antibody or antigen-binding fragment specifically binds to a region comprising about 12 or more cysteine residues of the isolated polypeptide of  claim 1 .  
     
     
         17 . The TgAMA-1 binding polypeptide of  claim 14 , wherein the binding polypeptide blocks entry of  Toxoplasma  parasite into a cell.  
     
     
         18 . An isolated anti-idiotype antibody that selectively binds to the TgAMA-1 binding polypeptide of  claim 14 .  
     
     
         19 . A method for reducing the likelihood of or treating a  toxoplasma  infection, comprising: 
 administering to a subject in need of such treatment, an effective amount of a TgAMA-1 binding polypeptide of  claim 14  to treat the  toxoplasma  infection.    
     
     
         20 . The composition of  claim 10 , wherein the composition is a proteosome vaccine.