Methods of treating and preventing staphylococcus aureus infections and associated conditions

Abstract

The present invention relates to methods and compositions for preventing and treating Staphylococcus aureus in a subject. Therapeutic compositions of the present invention comprise leukocidin E and/or D proteins or polypeptides and anti-leukocidin E and/or D antibodies. The invention further relates to methods of identifying inhibitors of LukE/D cytotoxicity and inhibitors of LukE/D-leukocyte binding.

1 . (canceled) 
     
     
         2 . A composition comprising:
 a Leukocidin E (LukE) polypeptide, said LukE polypeptide comprising an amino acid sequence having 80% to 99% sequence identity to the sequence of amino acid residues 29-311 of SEQ ID NO: 11; and   a pharmaceutically acceptable carrier.   
     
     
         3 . The composition of  claim 2 , wherein the sequence of the LukE polypeptide comprises 90% to 99% sequence identity to the sequence of amino acid residues 29-311 of SEQ ID NO: 11. 
     
     
         4 . The composition of  claim 2 , wherein the sequence of the LukE polypeptide comprises 95% to 99% sequence identity to the sequence of amino acid residues 29-311 of SEQ ID NO: 11. 
     
     
         5 . The composition of  claim 2  further comprising:
 a Leukocidin D (LukD) polypeptide, said LukD polypeptide comprising the amino acid sequence of amino acid residues 29-327 of SEQ ID NO: 22 or a fragment thereof. 
 
     
     
         6 . The composition of  claim 2  further comprising:
 an adjuvant. 
 
     
     
         7 . The composition of  claim 6  wherein the adjuvant is selected from the group consisting of flagellin, Freund's complete adjuvant, Freund's incomplete adjuvant, aluminum hydroxide, lysolecithin, pluronic polyols, polyanions, peptides, oil emulsion, dinitrophenol, iscomatrix, and liposome polycation DNA particles. 
     
     
         8 . A composition comprising:
 a Leukocidin D (LukD) polypeptide, said LukD polypeptide comprising an amino acid sequence having 80% to 99% sequence identity to the sequence of amino acid residues 29-327 of SEQ ID NO: 22; and   a pharmaceutically acceptable carrier.   
     
     
         9 . The composition of  claim 8 , wherein the sequence of the LukD polypeptide comprises 90% to 99% sequence identity to the sequence of amino acid residues 29-327 of SEQ ID NO: 22. 
     
     
         10 . The composition of  claim 8 , wherein the sequence of the LukD polypeptide comprises 95% to 99% sequence identity to the sequence of amino acid residues 29-327 of SEQ ID NO: 22. 
     
     
         11 . The composition of  claim 8  further comprising:
 a Leukocidin E (LukE) polypeptide, said LukE polypeptide comprising the amino acid sequence of amino acid residues 29-311 of SEQ ID NO: 11. 
 
     
     
         12 . The composition of  claim 8  further comprising:
 an adjuvant. 
 
     
     
         13 . The composition of  claim 12 , wherein the adjuvant is selected from the group consisting of flagellin, Freund's complete adjuvant, Freund's incomplete adjuvant, aluminum hydroxide, lysolecithin, pluronic polyols, polyanions, peptides, oil emulsion, dinitrophenol, iscomatrix, and liposome polycation DNA particles.