Conjugate vaccines for the prevention of dental caries

Abstract

The present invention provides glucan-based compositions and methods for stimulating an immune response against mutans streptococci components and vaccines and methods for the treatment and prevention of dental caries. In a preferred embodiment, a glucan polymer, preferably WSG, is covalently bound to one or more T cell-dependent antigens to form a conjugate vaccine. The T cell-dependent antigen preferably contains epitopes of one or more mutans streptococcal proteins, such as a glucosyltransferase. Moreover, one or more moieties, including haptens, may be conjugated to the glucan or to the glucan-T cell-dependent composition. In a preferred embodiment, these moieties are peptides which contain immunogenic epitopes corresponding to components of a mutans streptococcus.

1 . An immunogenic composition comprising: 
 (a) at least one isolated or purified streptococcal glucan, and    (b) at least one T cell-dependent (TD) antigen, wherein said TD antigen is covalently conjugated to the glucan;    wherein the immunogenic composition elicits antibodies to both the streptococcal glucan and the TD antigen.    
     
     
         2 . The immunogenic composition of  claim 1 , wherein the TD antigen is selected from full-length glucosyltransferase (GTF), a recombinant GTF fusion protein, and an immunogenic fragment of a GTF.  
     
     
         3 . The immunogenic composition of  claim 2 , wherein said full-length GTF is from a cariogenic streptococcal  mutans.    
     
     
         4 . The immunogenic composition of  claim 2 , wherein said full-length GTF is from a  S. sobrinus.    
     
     
         5 . The immunogenic composition of  claim 2 , wherein said full-length GTF is from a  S. mutans.    
     
     
         6 . The immunogenic composition of  claim 1 , wherein the glucan is water soluble glucan (WSG).  
     
     
         7 . The immunogenic composition of  claim 1 , wherein the streptococcal glucan is from  S. mutans.    
     
     
         8 . The immunogenic composition of  claim 1 , wherein the streptococcal glucan is from  S. sobrinus.    
     
     
         9 . The immunogenic composition of  claim 1 , wherein the TD antigen induces antibodies that specifically bind to at least one epitope of a  mutans streptococcus.    
     
     
         10 . The immunogenic composition of  claim 1 , wherein the antibodies inhibit the catalytic or glucan binding activity of a glucosyltransferase (GTF).  
     
     
         11 . The immunogenic composition of  claim 1 , wherein the antibodies inhibit the binding properties of a glucan binding protein.  
     
     
         12 . The immunogenic composition of  claim 1 , wherein the antibodies inhibit the binding properties of a bacterial adhesion protein, AgI/II.  
     
     
         13 . The immunogenic composition of  claim 1 , further comprising one or more additional moieties conjugated to the glucan, to the TD antigen, or to both, wherein the additional moiety is selected from a hapten, TD antigen, Type 2 T cell-independent (TI-2) antigen, protein, peptide, detoxified lipopolysaccharide, carbohydrate, or lipid.  
     
     
         14 . The immunogenic composition of  claim 1 , wherein the glucan is covalently conjugated to the moiety through a spacer, linker, amino acid, peptide, protein, hapten, or a T-cell dependent (TD) antigen.  
     
     
         15 . An immunogenic composition comprising: 
 (a) an isolated or purified Type 2 T cell-independent (TI) antigen, and    (b) at least one T cell-dependent (TD) antigen, wherein said TD antigen is covalently conjugated to the TI-2 antigen;    wherein the immunogenic composition induces    (i) IgA and IgG antibodies that specifically bind to at least one protein component of a  mutans streptococcus  and;    (ii) IgA and IgG antibodies that specifically bind to at least one glucan of a  mutans streptococcus.      
     
     
         16 . The immunogenic composition of  claim 15 , wherein the TD antigen comprises at least one antigenic epitope of a  mutans streptococcus.    
     
     
         17 . The immunogenic composition of  claim 16 , wherein the TD antigen is selected from a full-length glucosyltransferase (GTF), a recombinant GTF fusion protein, and an immunogenic fragment of a GTF.  
     
     
         18 . The immunogenic composition of  claim 17 , wherein said full-length GTF is from a cariogenic streptococcal  mutans.    
     
     
         19 . The immunogenic composition of  claim 17 , wherein said full-length GTF is from a  S. sobrinus.    
     
     
         20 . The immunogenic composition of  claim 17 , wherein said full-length GTF is from a  S. mutans.    
     
     
         21 . The immunogenic composition of  claim 15 , wherein the TI-2 antigen is a high molecular weight bacterial polysaccharide.  
     
     
         22 . The immunogenic composition of  claim 15 , wherein the TI-2 antigen is a dextran.  
     
     
         23 . The immunogenic composition of  claim 15 , wherein the TI-2 antigen is a glucose polymer containing at least one of α-1,3 or α-1,6 glucoside linkage.  
     
     
         24 . The immunogenic composition of  claim 15 , further comprising one or more additional moieties conjugated to the TI-2 antigen, to the TD antigen, or to both, wherein the additional moiety is selected from a hapten, TD antigen, TI-2 antigen, protein, peptide, detoxified lipopolysaccharide, carbohydrate, or lipid.  
     
     
         25 . The immunogenic composition of  claim 15 , wherein the TD antigen induces antibodies that specifically bind to at least one epitope of a  mutans streptococcus.    
     
     
         26 . The immunogenic composition of  claim 15 , wherein the TI-2 antigen is covalently conjugated to the moiety through a spacer, linker, amino acid, peptide, protein, hapten, or a T-cell dependent (TD) antigen.  
     
     
         27 . A vaccine, comprising an immunostimulatory amount of the composition of  claim 1  in a pharmaceutically acceptable carrier or delivery vehicle.