Glycolipid compositions and methods of use

Abstract

The invention provides immunostimulatory glycolipids and compositions thereof and methods of use thereof.

1 . A glycolipid comprising
 a tri-acylated, tetra-acylated or penta-acylated diglucosamine conjugated to an oligosaccharide.   
     
     
         2 . (canceled) 
     
     
         3 . The glycolipid of  claim 1 , wherein the tri-acylated, tetra-acylated or penta-acylated diglucosamine comprises acyl chains ranging in length from 14-17 carbons. 
     
     
         4 . (canceled) 
     
     
         5 . The glycolipid of  claim 1 , substantially free of other components found in a  B. fragilis  capsule, substantially free of LPS, substantially free of polysaccharide, in purified form, in an isolated form, and/or in a lyophilized form. 
     
     
         6 - 9 . (canceled) 
     
     
         10 . The glycolipid of  claim 1 , in a micelle form or a liposome form. 
     
     
         11 - 12 . (canceled) 
     
     
         13 . The glycolipid of  claim 1 , obtained or derived from  B. fragilis  cells that overexpress PSA relative to polysaccharide B (PSB), PSC, PSD, PSE, PSF, PSG and PSH. 
     
     
         14 . The glycolipid of  claim 1 , wherein at least one acyl chain is unmodified. 
     
     
         15 - 17 . (canceled) 
     
     
         18 . The glycolipid of  claim 1 , wherein at least one acyl chain is C16:0-OH; C17:0-OH; C14:0; C15:0; N-substituted; or O-substituted. 
     
     
         19 - 24 . (canceled) 
     
     
         25 . The glycolipid of  claim 1 , wherein the diglucosamine is phosphorylated. 
     
     
         26 . The glycolipid of  claim 1 , wherein the diglucosamine is conjugated to the oligosaccharide by an acid-labile bond. 
     
     
         27 . (canceled) 
     
     
         28 . The glycolipid of  claim 1 , wherein the oligosaccharide contains 3-10 sugars. 
     
     
         29 . The glycolipid of  claim 1 , wherein the oligosaccharide comprises galactose and/or glucose and/or fucose residues and/or 1 to 2 KDO residues. 
     
     
         30 . (canceled) 
     
     
         31 . A composition comprising the glycolipid of  claim 1 , and any one selected from the group consisting of:
 (i) a detergent or a bile salt;   (ii) a non-naturally occurring preservative;   (iii) a non-naturally occurring stabilizer;   (iv) human albumin, phenol, glycerin or glycine;   (v) thimerosal, aluminum hydroxide, benzethonium chloride, formaldehyde, formalin, glutaraldehyde, potassium phosphate, aluminum potassium sulfate, bovine extract, calf serum, ammonium sulfate, aluminum phosphate, non-human cells, Vero (monkey kidney) cells, human cells, MRC-5 (human diploid) cells, and/or MRC-5 cellular proteins;   (vi) a lipidated polysaccharide A (PSA), wherein the lipidated polysaccharide A (PSA) and the glycolipid are in a 4:1 to 20:1 ratio (w/w);   (vii) a lipidated polysaccharide A (PSA), wherein there is at least 0.5% (w/w) of the glycolipid;   (viii) an antigen; and   (ix) an antigen and a lipidated PSA.   
     
     
         32 . The composition of  claim 31 , wherein the detergent or bile salt is present at or less than 1%, 0.5% or 0.1% (weight of detergent or bile salt as a percentage of weight of glycolipid). 
     
     
         33 - 36 . (canceled) 
     
     
         37 . The composition of  claim 31 , formulated for parenteral administration or oral administration. 
     
     
         38 - 48 . (canceled) 
     
     
         49 . The composition of  claim 31  wherein the antigen is a bacterial antigen, attenuated bacteria, a viral antigen, an attenuated virus, a fungal antigen, a mycobacterial antigen, a parasitic antigen, a cancer antigen, a human protein, or a human polysaccharide. 
     
     
         50 - 82 . (canceled) 
     
     
         83 . A micelle consisting essentially of glycolipid of  claim 1 . 
     
     
         84 . A composition comprising
 a micelle consisting essentially of glycolipid of  claim 1  and   a detergent or bile salt.   
     
     
         85 . The composition of  claim 84 , wherein the detergent or bile salt is present in a pharmaceutically acceptable amount. 
     
     
         86 . The composition of  claim 84 , wherein the composition is a pharmaceutical composition. 
     
     
         87 . The composition of  claim 84 , formulated for parenteral administration. 
     
     
         88 - 95 . (canceled)