Cholesterol-containing compounds and their use as immunogens against borrelia burgdorferi

Abstract

Unique compounds that can be used for inducing an immune response to Borrelia burgdorferi in a subject by administering a therapeutically effective amount of the glycolipid to the subject. Such administration is particularly useful for preventing or treating Lyme disease in a subject. The compounds(s), and therapeutically acceptable salts thereof, may be formulated into pharmaceutical or immunogenic compositions.

1 . A purified compound having a formula B below, or a pharmaceutically acceptable salt or complex thereof, wherein the compound of formula B comprises 
     
       
         
         
             
             
         
       
       wherein “16” represents the number of carbon atoms in a palmitoyl group shown in the formula. 
     
   
   
       2 . The compound of  claim 1 , wherein the compound is isolated from  B. burgdorferi.    
   
   
       3 . A pharmaceutical composition comprising a therapeutically effective amount of the purified compound of  claim 1  and a pharmaceutically acceptable carrier. 
   
   
       4 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula B, or a pharmaceutically acceptable salt or complex thereof, conjugated to at least one protein carrier, wherein the compound of formula B comprises 
     
       
         
         
             
             
         
       
       wherein “16” represents the number of carbon atoms in a palmitoyl group shown in the formula. 
     
   
   
       5 . A method of inducing an immune response to  B. burgdorferi  in a subject, comprising administering a therapeutically effective amount of the purified compound of  claim 1  to the subject, thereby inducing the immune response. 
   
   
       6 . A method of preventing or treating Lyme disease in a subject, comprising administering to a subject a therapeutically effective amount of the purified compound of  claim 1 , thereby preventing or treating Lyme disease in the subject. 
   
   
       7 . A purified cholesteryl 6-O-acyl-β-D-galactopyranoside, wherein
 (i) the acyl moiety is derived from an organic fatty acid containing from 1 to 25 carbon atoms;   (ii) the cholesteryl and the galactopyranoside ring structures optionally include, at any ring position, substituent groups selected from alkyl, an acyl group derived from a fatty acid, carboxyl, aryl, alkoxy, heterocyclic, halogen and amino groups; and   (iii) the O bridging the cholesteryl and the galactopyranoside rings is optionally replaced by an alkyl radical or S.   
   
   
       8 . The compound of  claim 7  wherein the optional modifications (ii) and (iii) are not included. 
   
   
       9 . The compound of  claim 7  which is 3-O-(6-O-palmitoyl-β-D-galactopyranosyl) cholesterol. 
   
   
       10 . The compound of  claim 7  which is 3-O-(6-O-oleoyl-β-D-galactopyranosyl) cholesterol. 
   
   
       11 . A pharmaceutical composition comprising a therapeutically effective amount of a cholesteryl 6-O-acyl-β-D-galactopyranoside conjugated to at least one protein carrier, wherein
 (i) the acyl moiety is derived from an organic fatty acid containing from 1 to 25 carbon atoms;   (ii) the cholesteryl and the galactopyranoside ring structures optionally include, at any ring position, substituent groups selected from alkyl, an acyl group derived from a fatty acid, carboxyl, aryl, alkoxy, heterocyclic, halogen and amino groups; and   (iii) the O bridging the cholesteryl and the galactopyranoside rings is optionally replaced by an alkyl radical or S.   
   
   
       12 . A method of inducing an immune response to  B. burgdorferi  in a subject, comprising administering a therapeutically effective amount of the purified compound of  claim 7  to the subject, thereby inducing the immune response. 
   
   
       13 . A method of preventing or treating Lyme disease in a subject, comprising administering to a subject a therapeutically effective amount of the purified compound of  claim 7 , thereby preventing or treating Lyme disease in the subject. 
   
   
       14 . An immunogenic composition comprising 3-O-(6-O-palmitoyl-β-D-galactopyranosyl) cholesterol and at least one additive. 
   
   
       15 . An isolated mixture comprising 3-O-(6-O-palmitoyl-β-D-galactopyranosyl) cholesterol and 3-O-(6-O-oleoyl-β-D-galactopyranosyl) cholesterol. 
   
   
       16 . The mixture of  claim 15 , wherein the mixture includes less than one weight percent nucleic acids and less than one percent proteins.