Activation of HCV-specific T cells

Abstract

The invention provides a method of activating hepatitis C virus (HCV)-specific T cells, including CD4 + and CD8 + T cells. HCV-specific T cells are activated using fusion proteins comprising HCV NS3, NS4, NS5 a , and NS5 b polypeptides, polynucleotides encoding such fusion proteins, or polypeptide or polynucleotide compositions containing the individual components of these fusions. The method can be used in model systems to develop HCV-specific immunogenic compositions, as well as to immunize a mammal against HCV.

1 . A composition comprising:
 (a) a fusion protein comprising HCV polypeptides, wherein the HCV polypeptides consist of an NS3, an NS4, an NS5a, and NS5b polypeptide of a hepatitis C virus (HCV) and optionally a core polypeptide; and   (b) a polynucleotide encoding an HCV E1E2 complex,   
       wherein the composition stimulates an immune response to HCV. 
     
     
         2 . The composition of  claim 1 , wherein at least one of the HCV polypeptides is derived from a different strain of HCV than the other HCV polypeptides. 
     
     
         3 . The composition of  claim 1 , further comprising a pharmaceutically acceptable excipient. 
     
     
         4 . The composition of  claim 3 , further comprising an adjuvant. 
     
     
         5 . The composition of  claim 3 , further comprising a CpG oligonucleotide. 
     
     
         6 . The composition of  claim 3 , wherein said fusion protein is adsorbed to or entrapped within a microparticle or ISCOM. 
     
     
         7 . A composition comprising a hepatitis C virus (HCV) polynucleotide encoding an HCV E1E2 complex, HCV polypeptides, and a pharmaceutically acceptable excipient, wherein the HCV polypeptides consist of:
 (a) an isolated and purified NS3 polypeptide;   (b) an isolated and purified NS4;   (c) an isolated and purified NS5a polypeptide;   (d) an isolated and purified NS5b polypeptide; and optionally,   (e) an isolated and purified core polypeptide,   
       wherein the composition stimulates an immune response to HCV. 
     
     
         8 . The composition of  claim 7 , further comprising an adjuvant. 
     
     
         9 . The composition of  claim 7 , further comprising a CpG oligonucleotide. 
     
     
         10 . The composition of  claim 7 , wherein one or more of said HCV polypeptides is adsorbed to or entrapped within a microparticle or ISCOM. 
     
     
         11 . A method of activating T cells of a vertebrate subject which recognize an epitope of an HCV polypeptide, comprising the step of:
 administering the composition of  claim 1  to said vertebrate subject, whereby a population of activated T cells recognizes an epitope of the NS3, NS4, NS5a, NS5b and/or core polypeptides.   
     
     
         12 . A method of activating T cells of a vertebrate subject which recognize an epitope of an HCV polypeptide, comprising the step of:
 administering the composition of  claim 4  to said vertebrate subject, whereby a population of activated T cells recognizes an epitope of the NS3, NS4, NS5a, NS5b and/or core polypeptides.   
     
     
         13 . A method of activating T cells of a vertebrate subject which recognize an epitope of an HCV polypeptide, comprising the step of:
 administering the composition of  claim 5  to said vertebrate subject, whereby a population of activated T cells recognizes an epitope of the NS3, NS4, NS5a, NS5b and/or core polypeptides.   
     
     
         14 . A method of activating T cells of a vertebrate subject which recognize an epitope of an HCV polypeptide, comprising the step of:
 administering the composition of  claim 6  to said vertebrate subject, whereby a population of activated T cells recognizes an epitope of the NS3, NS4, NS5a, NS5b and/or core polypeptides.   
     
     
         15 . A method of activating T cells of a vertebrate subject which recognize an epitope of an HCV polypeptide, comprising the step of:
 administering the composition of  claim 7  to said vertebrate subject, whereby a population of activated T cells recognizes an epitope of the NS3, NS4, NS5a, NS5b and/or core polypeptides.