H. Pylori Lipopolysaccharide Outer Core Epitope

Abstract

Helicobacter pylori , one of the most common human pathogens, is associated with the development of human chronic gastritis, peptic ulcers and gastric cancer. The invention relates to a α1,6-glucan-containing Helicobacter pylori compound comprising the structure of Formula I: wherein R is a α-DDHep-3-α-L-Fuc-3-β-GlcNAc trisaccharide substituted with an α1,6-glucan linked to an α1,3-DD-heptan, and wherein the last DD-Hep residue of α1,3-DD-heptan is capped with β-GlcNAc residue. Compositions comprising the compound, uses of the compound, and antibodies raised against the compound are also described.

1 . An immune antiserum isolated from an individual comprising antibodies recognizing an α1,6-glucan-containing  Helicobacter pylori  compound comprising the structure of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein the R is a α-DDHep-3-α-L-Fuc-3-β-GlcNAc trisaccharide substituted with an α1,6-glucan comprising from 4 to 12 α1,6-linked glucose residues linked to an α1,3-DD-heptan, wherein the last DD-Hep residue of the α1,3-DD-heptan is capped with β-GlcNAc residue. 
     
     
         2 . The immune antiserum of  claim 1 , wherein in the structure of Formula I, the heptan moiety comprises from 2 to 6 α1,3-linked heptose residues. 
     
     
         3 . The immune antiserum of  claim 1 , wherein in the structure of Formula I, R comprises 
       
         
           
           
               
               
           
         
       
       where β-GlcNAc residue L is linked to O-2 of Hep G, n=1 to 11, and m=0 to 4. 
     
     
         4 . The immune antiserum of  claim 3 , wherein in the structure of Formula I, n=9. 
     
     
         5 . The immune antiserum of  claim 3 , wherein in the structure of Formula I, m=2. 
     
     
         6 . The immune antiserum of  claim 1 , wherein the structure of Formula I further comprises a lipid A moiety covalently attached to the Kdo residue C. 
     
     
         7 . The immune antiserum of  claim 6 , wherein in the structure of Formula I, the lipid A molecule is O-deacylated or is cleaved through hydrolysis of the ketosidic linkage of the Kdo residue. 
     
     
         8 . The immune antiserum of  claim 1 , wherein the compound is isolated or purified from  H. pylori  strain HP0826::Kan. 
     
     
         9 . The immune antiserum of  claim 1 , the antiserum comprising an IgG recognizing an α1,6-linked glucan epitope in homologous and heterologous typeable and non-typeable mutant and wild-type strains of  H. pylori.    
     
     
         10 . The immune antiserum of  claim 9 , wherein the IgG causes complement-mediated bacteriolysis of mutant and wild-type α1,6-glucan-expressing  H. pylori  strains.