Heat shock protein-based vaccines and immunotherapies

Abstract

The present invention relates to methods and compositions for inducing an immune response in a subject, wherein the subject is administered an effective amount of at least one heat shock protein in combination with one or more defined target antigens. These methods and compositions may be used in the treatment of infectious diseases and cancers.

1 . A composition for inducing a therapeutic immune response in a subject, comprising: 
 (a) a target antigen; and    (b) a heat shock protein;    wherein the target antigen and the heat shock protein are combined in vitro under conditions wherein binding of target antigen to heat shock protein occurs to form a target antigen/heat shock protein complex;    wherein the administration of the target antigen/heat shock protein complex to the subject induces an immune response comprising a cytotoxic cellular component.    
     
     
         2 . The composition of  claim 1 , wherein the heat shock protein is hsp70.  
     
     
         3 . The composition of  claim 1 , wherein the heat shock protein is gp96.  
     
     
         4 . The composition of  claim 1 , wherein the heat shock protein is hsp40.  
     
     
         5 . The composition of  claim 1 , wherein the heat shock protein is BiP.  
     
     
         6 . The composition of any of  claims 1  to  5 , wherein the target antigen is a hybrid antigen.  
     
     
         7 . The composition according to  claim 6  wherein the hybrid antigen comprises an antigenic domain derived from a first source and a binding domain which binds to a heat shock protein from a second source different from the first source.  
     
     
         8 . The composition of  claim 7 , wherein the binding domain comprises at least a heptameric region having the sequence  
       HyXHyXHyXHy  
       where Hy represents a hydrophobic amino acid residue and X is any amino acid.  
     
     
         9 . The composition of  claim 7 , wherein the binding domain comprises a region having the sequence 
 His Trp Asp Phe Ala Trp Pro Trp [Seq. ID No. 1]   
     
     
         10 . A composition for inducing a therapeutic immune response in a subject, comprising: 
 (a) a nucleic acid molecule comprising a region encoding a target antigen operably linked to a promoter element; and    (b) a nucleic acid molecule comprising a region encoding a heat shock protein operably linked to a promoter element;    wherein the introduction of the nucleic acids of (a) and (b) into a cell result in the binding of target antigen to heat shock protein.    
     
     
         11 . The composition of  claim 10 , wherein the nucleic acid molecules of (a) and (b) are comprised in the same vector.  
     
     
         12 . The composition of  claim 10  or  11 , wherein the heat shock protein is hsp70.  
     
     
         13 . The composition of  claim 10  or  11 , wherein the heat shock protein is gp96.  
     
     
         14 . The composition of  claim 10  or  11 , wherein the heat shock protein is hsp40.  
     
     
         15 . The composition of  claim 10  or  11 , wherein the heat shock protein is BiP.  
     
     
         16 . The composition of any of  claims 10  to  15 , wherein the target antigen is a hybrid antigen.  
     
     
         17 . The composition according to  claim 16 , wherein the hybrid antigen comprises an antigenic domain derived from a first source and a binding domain which binds to a heat shock protein. from a second source different from the first source.  
     
     
         18 . The composition of  claim 17 , wherein the binding domain comprises at least a heptameric region having the sequence  
       HyXHyXHyXHy  
       where Hy represents a hydrophobic amino acid residue and X is any amino acid.  
     
     
         19 . The composition of  claim 17 , wherein the binding domain comprises a region having the sequence 
 His Trp Asp Phe Ala Trp Pro Trp [Seq. ID No. 1]   
     
     
         20 . A method of inducing an immune response in a subject in need of such treatment, comprising administering to the subject a therapeutically effective amount of the composition of any of  claims 1  to  19 .  
     
     
         21 . A hybrid peptide comprising: 
 (a) an antigenic domain derived from a first source; and    (b) a binding domain which binds to a heat shock protein, said binding domain being derived from a second source different from the first source.    
     
     
         22 . The hybrid peptide of  claim 21 , wherein the antigenic domain is derived from a virus, a parasite, a mycoplasma, a fungus or a bacterium.  
     
     
         23 . The hybrid peptide of any of claims  21 - 22 , wherein the antigenic domain elicits an immune response to a neoplastic disease.  
     
     
         24 . The hybrid peptide of  claim 23 , wherein the neoplastic disease is selected from among a sarcoma, a lymphoma, a carcinoma, a leukemia and a melanoma.  
     
     
         25 . The hybrid peptide of any of  claims 21  to  24 , wherein the binding domain comprises at least a heptameric region having the sequence  
       HyXHyXHyXHy  
       where Hy represents a hydrophobic amino acid residue and X is any amino acid.  
     
     
         26 . The hybrid peptide of any of  claim 21  to  24 , wherein the binding domain comprises a region having the sequence 
 His Trp Asp Phe Ala Trp Pro Trp [Seq. ID No. 1].  
 
     
     
         27 . The hybrid peptide of any of  claims 21  to  24 , wherein the binding domain comprises at least a pentapeptide region selected from among 
 Gln Lys Arg Ala Ala [Seq. ID No. 5], and  
 Arg Arg Arg Ala Ala [Seq. ID No. 6].  
 
     
     
         28 . A polynucleotide construct comprising: 
 (a) a region encoding a hybrid peptide comprising an antigenic domain derived from a first source; and a binding domain which binds to a heat shock protein said binding domain being derived from a second source different from the first source;    (b) a promoter effective to promote expression on the hybrid peptide in mammalian cells.    
     
     
         29 . The polynucleotide construct of  claim 28 , wherein the antigenic domain is derived from a virus, a parasite, a mycoplasma, a fungus or a bacterium.  
     
     
         30 . The polynucleotide construct of  claim 28 , wherein the antigenic domain elicits an immune response to a neoplastic disease.  
     
     
         31 . The polynucleotide construct of  claim 30 , wherein the neoplastic disease is selected from among a sarcoma, a lymphoma, a carcinoma, a leukemia and a melanoma.  
     
     
         32 . The polynucleotide construct of any of  claims 28  to  31 , wherein the binding domain comprises at least a heptameric region having the sequence  
       HyXHyXHyXHy  
       where Hy represents a hydrophobic amino acid residue and X is any amino acid.  
     
     
         33 . The polynucleotide construct of any of  claims 28  to  31 , wherein the binding domain comprises a region having the sequence 
 His Trp Asp Phe Ala Trp Pro Trp [Seq. ID No. 1].  
 
     
     
         34 . The polynucleotide construct of any of claim s  28  to  31 , wherein the binding domain comprises at least a pentapeptide region selected from among 
 Gln Lys Arg Ala Ala [Seq. ID No. 5], and  
 Arg Arg Arg Ala Ala [Seq. ID No. 6].