Leukotoxin e/d as a new anti-inflammatory agent and microbicide

Abstract

The present invention relates to methods for preventing or treating Human Immunodeficiency Virus (HIV) infection, inflammatory conditions, and graft-versus-host-disease (GVHD) in a subject. Therapeutic compositions of the present invention comprise Leukocidin E (LukE) and/or D proteins or polypeptides. The invention further relates to methods of treating Staphylococcus aureus infection by administering a composition comprising a CCR5 antagonist or any molecule that blocks LukE/D interaction with CCR5 + cells in an amount effective to treat the S. aureus infection in the subject.

1 . A method of preventing or treating Human Immunodeficiency Virus (HIV) infection in a subject comprising:
 administering a composition comprising an isolated Leukocidin E (LukE) protein, or polypeptide thereof, and an isolated Leukocidin D (LukD) protein, or polypeptide thereof, in an amount effective to prevent or treat HIV infection in the subject.   
     
     
         2 . The method of  claim 1 , wherein the composition comprises an isolated LukE protein comprising an amino acid sequence of SEQ ID NO:11 or an amino acid sequence having at least 70% sequence similarity to SEQ ID NO:11. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the composition comprises an isolated LukD protein comprising an amino acid sequence of SEQ ID NO:22 or an amino acid sequence having at least 70% sequence similarity to SEQ ID NO:22. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1  further comprising:
 administering one or more antiviral or other agent useful in the treatment of HIV in combination with the composition comprising an isolated LukE protein, or polypeptide thereof, and an isolated LukD protein, or polypeptide thereof. 
 
     
     
         7 .- 8 . (canceled) 
     
     
         9 . A composition comprising:
 a therapeutically effective amount of an isolated staphylococcal leukocidin E (LukE) protein or polypeptide thereof, and an isolated staphylococcal leukocidin D (LukD) protein or polypeptide thereof.   
     
     
         10 . The composition of  claim 9 , wherein the composition comprises an isolated LukE protein comprising an amino acid sequence of SEQ ID NO:11 or an amino acid sequence having at least 70% sequence similarity to SEQ ID NO:11. 
     
     
         11 . The composition of  claim 9 , wherein the composition comprises an isolated LukE polypeptide comprising amino acid residues 48-291 of SEQ ID NO:11. 
     
     
         12 . The composition of  claim 9 , wherein the composition comprises an isolated LukD protein comprising an amino acid sequence of SEQ ID NO:22 or an amino acid sequence having at least 70% sequence similarity to SEQ ID NO:22. 
     
     
         13 . The composition of  claim 9 , wherein the composition comprises an isolated LukD polypeptide comprising amino acid residues 46-307 of SEQ ID NO:22. 
     
     
         14 . The composition of  claim 39 , wherein the lubricant is selected from the group consisting of cetyl esters wax, hydrogenated vegetable oil, magnesium stearate, methyl stearate, mineral oil, polyoxyethylene-polyoxypropylene copolymer, polyethylene glycol, polyvinyl alcohol, sodium lauryl sulfate or white wax, and a mixture of two or more thereof. 
     
     
         15 . The composition of  claim 39 , wherein the antimicrobial agent is selected from the group consisting of propylene glycol, methyl paraben, propyl paraben, and a mixture of two or more thereof. 
     
     
         16 . The composition of  claim 39 , wherein the antioxidant is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, edetate disodium, and a mixture of two or more thereof. 
     
     
         17 . The composition of  claim 39 , wherein the humectant is selected from the group consisting of ethylene glycol, glycerin, sorbitol, or a mixture of two or more thereof. 
     
     
         18 . The composition of  claim 39 , wherein the emulsifier is selected from the group consisting of carbomer, polyoxyethylene-10-stearyl ether, polyoxyethylene-20-stearyl ether, cetostearyl alcohol, cetyl alcohol, cholesterol, diglycol stearate, glyceryl monostearate, glyceryl stearate, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, lanolin, polyoxyethylene lauryl ether, methyl cellulose, polyoxyethylene stearate, polysorbate, propylene glycol monostearate, sorbitan esters, stearic acid, and a mixture of two or more thereof. 
     
     
         19 . The composition of  claim 9 , wherein said composition is formulated for topical administration. 
     
     
         20 . The composition of  claim 9 , wherein said composition is formulated for vaginal and/or rectal administration 
     
     
         21 . The composition of  claim 9 , wherein said composition is formulated as an oral rinse. 
     
     
         22 . A method of preventing HIV infection in a subject, said method comprising:
 providing a composition of  claim 9 , and   contacting tissue of the subject with the composition under conditions effective to block HIV infectivity of cells in the tissue, thereby inhibiting HIV infection in the subject.   
     
     
         23 . (canceled) 
     
     
         24 . A method of treating an inflammatory condition in a subject comprising:
 administering a composition comprising an isolated LukE protein, or polypeptide thereof, and an isolated LukD protein, or polypeptide thereof, in an amount effective to treat an inflammatory condition in the subject.   
     
     
         25 - 38 . (canceled) 
     
     
         39 . The composition of  claim 9  further comprising:
 one or more additional agents selected from the group consisting of a lubricant, an antimicrobial agent, a humectant, an emulsifier, a pharmaceutically acceptable carrier, and a mixture of two or more thereof.