Nucleotide vector, composition containing such vector, and vaccine for immunization against hepatitis

Abstract

Nucleotide vector composition containing such vector and vaccine for immunization against hepatitis. Nucleotide vector comprising at least one gene or one complementary DNA coding for at least a portion of a virus, and a promoter providing for the expression of such gene in muscle cells. The gene may be the S gene of the hepatitis B virus. A nucleotide vector composition when administered to even chronic HBV carriers is capable of breaking T cell tolerance to the surface antigens of hepatitis B virus. A vaccine preparation containing said bare DNA is injected into the host previously treated with a substance capable of inducing a coagulating necrosis of the muscle fibers.

1 . A nucleotide sequence comprising a promoter homologous to the host and another regulatory sequence for the expression of a gene or a DNA coding complement for S, preS 2 -S, or preS 1 -preS 2 -S. 
     
     
         2 . A vaccine comprising the nucleotide sequence according to  claim 1 . 
     
     
         3 . A composition capable of inducing a cytotoxic response comprising a gene or complementary DNA coding for at least a portion of a virus protein, which is expressed in the muscle cells, and an internal promoter. 
     
     
         4 . The composition of  claim 3 , wherein said gene is the S gene. 
     
     
         5 . The composition of  claim 3 , wherein said protein is the S, preS 2 -S, or preS 1 -preS 2 -S protein. 
     
     
         6 . A non-lipid pharmaceutical composition comprising at least one substance capable of inducing a coagulating necrosis of the muscle fibers and either a vector comprising a gene or complementary DNA coding for at least a portion of a virus protein, and a promoter allowing the expression of the gene in the muscle cells or a complete or partial nucleotide sequence comprising a promoter homologous to the host and another regulatory sequence for the expression of a gene or a DNA coding complement for S, preS 2 -S, or preS 1 -preS 2 -S. 
     
     
         7 . The composition of  claim 6 , wherein said gene is the S gene. 
     
     
         8 . The composition of  claim 6 , wherein said protein is the S, S-preS 2 , or S-preS 1 -preS 2  protein. 
     
     
         9 . The composition of any one of  claims 6  to  8 , wherein said composition is administered to a chronic HBV carrier. 
     
     
         10 . A composition for inducing a B and/or T cell response in chronic HBV carriers comprising a vector, wherein said vector comprises a gene or complementary DNA coding for at least a portion of a hepatitis B protein and a promoter. 
     
     
         11 . The composition of  claim 10 , wherein the B cell response is able to clear the circulating HBsAg. 
     
     
         12 . The composition of  claim 10 , wherein said gene or complementary DNA encodes a HBV protein selected from group consisting of pre-S2, pre-S1, S protein, and a part of pre-S2, pre-S1, or S protein. 
     
     
         13 . The composition of  claim 10 , wherein said gene or complementary DNA encodes a pre-S2 or pre-S1 protein of HBV and an S protein of HBV or a part of pre-S2 or pre-S1 protein and a part of S protein. 
     
     
         14 . A composition according to any one of  claims 10 ,  11 ,  12 , or  13  for inducing a T cell response. 
     
     
         15 . A process of treating chronic HBV carriers comprising administering to said chronic HBV carriers a therapeutically effective amount of the composition according to any one of  claims 10  to  13 . 
     
     
         16 . A recombinant plasmid containing a nucleotide sequence according to any one of  claims 10  to  13 , wherein said sequence encodes for the small and/or the middle forms of HBV surface protein.