Compositions isolated from M. vaccae and their use in the modulation of immune responses

Abstract

Polypeptides and polynucleotides isolated from Mycobacterium vaccae are provided, together with compositions comprising such polypeptides and polynucleotides, and methods for their use in the enhancement of immune responses to heterologous antigens.

1 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 6-9.  
     
     
         2 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) sequences having at least 75% identity to a sequence of SEQ ID NO: 6-9;    (b) sequences having at least 90% identity to a sequence of SEQ ID NO: 6-9; and    (c) sequences having at least 95% identity to a sequence of SEQ ID NO: 6-9, wherein the polypeptide is capable of eliciting and/or enhancing an immune response.    
     
     
         3 . An isolated polynucleotide encoding a polypeptide according to any one of claims  1  and  2 .  
     
     
         4 . An isolated polynucleotide comprising a sequence selected from the group consisting of: 
 (a) SEQ ID NO: 1-5;    (b) sequences having at least 75% identity to a sequence of SEQ ID NO: 1-5;    (c) sequences having at least 90% identity to a sequence of SEQ ID NO: 1-5; and    (d) sequences having at least 95% identity to a sequence of SEQ ID NO: 1-5.    
     
     
         5 . An expression vector comprising a polynucleotide according to  claim 4 .  
     
     
         6 . A host cell transformed with an expression vector according to  claim 5 .  
     
     
         7 . An immunogenic composition comprising at least one polypeptide according to any one of claims  1  and  2  and a heterologous antigen.  
     
     
         8 . The immunogenic composition of  claim 7 , wherein the heterologous antigen is selected from the group consisting of: tumor-specific antigens; infectious disease antigens; and autoantigens.  
     
     
         9 . An immunogenic composition comprising at least one polynucleotide according to  claim 4  and a heterologous antigen.  
     
     
         10 . The immunogenic composition of  claim 9 , wherein the heterologous antigen is selected from the group consisting of: tumor-specific antigens; infectious disease antigens; and autoantigens.  
     
     
         11 . A method for modulating an immune response in a patient, comprising administering an immunogenic composition according to any one of claims  7  and  9 .  
     
     
         12 . The method of  claim 11 , wherein the immune response is a Th1 response.  
     
     
         13 . The method of  claim 11 , wherein the immune response is a Th2 response.  
     
     
         14 . A method for enhancing a Th1-type immure response, comprising administering an isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) sequences of SEQ ID NO: 7 and 8;    (b) sequences having at least 75% identity to a sequence of SEQ ID NO: 7 and 8;    (c) sequences having at least 90% identity to a sequence of SEQ ID NO: 7 and 8; and    (d) sequences having at least 95% identity to a sequence of SEQ ID NO: 7 and 8.    
     
     
         15 . A method for enhancing a Th2-type immure response, comprising administering a polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) SEQ ID NO: 3;    (b) sequences having at least 75% identity to SEQ ID NO: 3;    (c) sequences having at least 90% identity to SEQ ID NO: 3; and    (d) sequences having at least 95% identity to SEQ ID NO: 3.    
     
     
         16 . A method for treating a disorder characterised by a Th2 immune response, comprising administering an isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) sequences of SEQ ID NO: 4 and 5;    (b) sequences having at least 75% identity to a sequence of SEQ ID NO: 4 and 5;    (c) sequences having at least 90% identity to a sequence of SEQ ID NO: 4 and 5; and    (d) sequences having at least 95% identity to a sequence of SEQ ID NO: 4 and 5.    
     
     
         17 . The method of  claim 16 , wherein the disorder is selected from the group consisting of:  mycobacterial  infections: sarcoidosis: asthma: allergic rhinitis: chronic graft versus host disease: systemic lupus erythematosus: systemic sclerosis: and cancer.  
     
     
         18 . A method for treating a disorder characterised by a Th1 immune response, comprising administering a polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) SEQ ID NO: 3;    (b) sequences having at least 75% identity to SEQ ID NO: 3;    (c) sequences having at least 90% identity to SEQ ID NO: 3; and    (d) sequences having at least 95% identity to SEQ ID NO: 3.    
     
     
         19 . The method of  claim 18 , wherein the disorder is selected from the group consisting of: tuberculosis; autoimmune thyroiditis; insulin-dependent diabetes mellitus; multiple sclerosis; Crohn's disease;  Helicobacter pylori -induced peptic ulcers; transplanted organ rejection and unexplained naturally-occurring abortions.  
     
     
         20 . A fusion protein comprising at least one polypeptide according to any one of claims  1  and  2  and a heterologous antigen.  
     
     
         21 . The fusion protein of  claim 20 , wherein the heterologous antigen is selected from the group consisting of: tumor-specific antigens; infectious disease antigens; and autoantigens.  
     
     
         22 . A method for modulating an immune response in a patient, comprising administering a fusion protein according to  claim 20.