Hepatitis c virus liposome vaccine

Abstract

The present invention provides a peptide-bound liposome wherein the peptide contains a partial amino acid sequence having a length of not less than 9 amino acids in the amino acid sequence of hepatitis C virus NS3 protein, has a length of 9 to 11 amino acids, and is capable of inducing cytotoxic T lymphocytes, the liposome contains a phospholipid containing an acyl group having 14 to 24 carbon atoms and one unsaturated bond or a hydrocarbon group having 14 to 24 carbon atoms and one unsaturated bond, and a liposome stabilizer, and the peptide is bound to the surface of the liposome; a cytotoxic T lymphocyte activator containing the peptide-bound liposome; and a hepatitis C virus vaccine.

1 . A peptide-bound liposome wherein the peptide comprises a partial amino acid sequence having a length of not less than 9 amino acids in the amino acid sequence of hepatitis C virus NS3 protein,
 has a length of 9 to 11 amino acids, and   is capable of inducing cytotoxic T lymphocytes;   the liposome comprises a phospholipid containing an acyl group having 14 to 24 carbon atoms and one unsaturated bond or a hydrocarbon group having 14 to 24 carbon atoms and one unsaturated bond, and a liposome stabilizer; and   the peptide is bound to the surface of the liposome.   
     
     
         2 . The peptide-bound liposome according to  claim 1 , wherein the phospholipid is a phospholipid containing an acyl group having 14 to 24 carbon atoms and one unsaturated bond. 
     
     
         3 . The peptide-bound liposome according to  claim 1 , wherein the acyl group is an oleoyl group. 
     
     
         4 . The peptide-bound liposome according to  claim 1 , wherein the phospholipid is at least one selected from diacylphosphatidylserine, diacylphosphatidylglycerol, diacylphosphatidic acid, diacylphosphatidylcholine, diacylphosphatidylethanolamine, succinimidyl-diacylphosphatidylethanolamine, and maleimido-diacylphosphatidylethanolamine. 
     
     
         5 . The peptide-bound liposome according to  claim 1 , wherein the liposome stabilizer is cholesterol. 
     
     
         6 . The peptide-bound liposome according to  claim 1 , wherein the peptide is bound to a phospholipid containing an acyl group having 14 to 24 carbon atoms and one unsaturated bond or a hydrocarbon group having 14 to 24 carbon atoms and one unsaturated bond, which phospholipid is contained in a phospholipid membrane constituting the liposome. 
     
     
         7 . The peptide-bound liposome according to  claim 1 , wherein the liposome has the following composition:
 (A) a phospholipid containing an acyl group having 14 to 24 carbon atoms and one unsaturated bond or a hydrocarbon group having 14 to 24 carbon atoms and one unsaturated bond 1 to 99.8 mol %;   (B) a liposome stabilizer 0.2 to 75 mol %.   
     
     
         8 . The peptide-bound liposome according to  claim 1 , wherein the liposome has the following composition:
 (I) an acidic phospholipid containing an acyl group having 14 to 24 carbon atoms and one unsaturated bond or a hydrocarbon group having 14 to 24 carbon atoms and one unsaturated bond 1 to 85 mol %;   (II) a neutral phospholipid containing an acyl group having 14 to 24 carbon atoms and one unsaturated bond or a hydrocarbon group having 14 to 24 carbon atoms and one unsaturated bond 0.01 to 80 mol %;   (III) a phospholipid containing an acyl group having 14 to 24 carbon atoms and one unsaturated bond or a hydrocarbon group having 14 to 24 carbon atoms and one unsaturated bond, which is bound with a peptide 0.2 to 80 mol %;   (IV) a liposome stabilizer 0.2 to 75 mol %.   
     
     
         9 . The peptide-bound liposome according to  claim 1 , wherein the partial amino acid sequence is an amino acid sequence shown by any of SEQ ID NOs: 1-3, 5 and 6. 
     
     
         10 . A cytotoxic T lymphocyte activator comprising the peptide-bound liposome according to  claim 1 . 
     
     
         11 . The cytotoxic T lymphocyte activator according to  claim 10 , further comprising CpG-DNA. 
     
     
         12 . A hepatitis C virus vaccine comprising the peptide-bound liposome according to  claim 1 . 
     
     
         13 . The hepatitis C virus vaccine according to  claim 12 , further comprising CpG-DNA. 
     
     
         14 . The hepatitis C virus vaccine according to  claim 12 , which is for the treatment of hepatitis C. 
     
     
         15 . The hepatitis C virus vaccine according to  claim 12 , which is for the prophylaxis of hepatitis C. 
     
     
         16 . A peptide comprising an amino acid sequence shown by SEQ ID NO: 1 or 2, having a length of 9-11 amino acids, and capable of inducing cytotoxic T lymphocyte. 
     
     
         17 . The peptide-bound liposome according to  claim 1 , which is for use for the prophylaxis or treatment of hepatitis C. 
     
     
         18 . A method for the prophylaxis or treatment of hepatitis C in a mammal, comprising administering a prophylactically or therapeutically effective amount of the peptide-bound liposome according to  claim 1  to the mammal. 
     
     
         19 . Use of the peptide-bound liposome according to  claim 1  for the production of a hepatitis C virus vaccine.