Synthetic anti-candida albicans oligosaccharide based vaccines

Abstract

The present invention provides methods of making and using immunogenic oligosaccharide compositions comprising native O-linked and S-linked oligosaccharides coupled to a protein carrier, wherein the resultant conjugate elicits a protectively immunogenic response. These compositions may be useful in vaccines against pathogenic Candida species.

1 - 17 . (canceled) 
   
   
       18 . A method of preventing or ameliorating infection by  Candida  species, which method comprises administering to a mammal an immunogenic effective amount of an anti-Candida species vaccine comprising a synthetic method that is an oligosaccharide selected from the group consisting of [β-D-mannopyranose-(1→2)-β-D-mannopyranose-(1→2)-β-D-mannopyranose and β-D-mannopyranose-(1→2)-β-D-mannopyranose, wherein each saccharide unit of said oligosaccharide is linked via an inter-glycosidic atom selected from the group consisting of oxygen and sulfur; and wherein the oligosaccharide is covalently method to a protein carrier through a linking group. 
   
   
       19 . The method of  claim 18 , wherein the oligosaccharide is β-D-mannopyranose-(1→2)-β-D-mannopyranose-(1→2)-β-D-mannopyranose. 
   
   
       20 . The method of  claim 18 , wherein the oligosaccharide is β-D-mannopyranose-(1→2)-β-D-mannopyranose. 
   
   
       21 . The method of  claim 20 , wherein at least one inter-glycosidic atom is sulfur. 
   
   
       22 . The method of  claim 21 , wherein the inter-glycosidic atom at a terminal non-reducing end of at least one of the saccharide units is sulfur. 
   
   
       23 . The method of  claim 18 , wherein the linking group is derived from diethyl squarate, polyoxyalkylene, succinic anhydride or maleic anhydride. 
   
   
       24 . The method of  claim 18 , wherein the linking group is derived from a heterobifunctional or homobifunctional cross coupling reagent. 
   
   
       25 . The method of  claim 18 , wherein the linking group is derived from a mammalian lipid mimic or a bacterial lipid mimic wherein the mammalian lipid mimic or a bacterial lipid mimic is functionalized to permit covalent attachment to a protein or peptide carrier. 
   
   
       26 . The method of  claim 25 , wherein the mammalian lipid mimic or a bacterial lipid mimic is selected from the group consisting of sphingosine, a diacyl glycerol, and a diphytanyl ether of glycerol. 
   
   
       27 . The method of  claim 18 , wherein the protein carrier is selected from the group consisting of bovine serum albumin, human serum albumin, tetanus toxoid, a recombinant outer membrane class 3 porn (rPorB) from group B  Neisseria meningitidis , and peptide carriers such as PADRE. 
   
   
       28 . The method of  claim 27 , wherein the protein carrier is tetanus toxoid or bovine serum albumin. 
   
   
       29 . The method of  claim 18 , wherein the  Candida  species is  Candida albicans.