Hepatitis virus core proteins as vaccine platforms and methods of use thereof

Abstract

The present invention relates to hepatitis virus core proteins and nucleic acids. In particular, the present invention provides compositions and methods comprising recombinant hepatitis virus core proteins or nucleic acids for use in vaccine formulations.

1 . An antigenic composition comprising a heterologous antigen inserted within the amino acid sequence of a hepadnavirus core antigen, wherein said heterologous antigen is 50 or fewer amino acids in length, and wherein said heterologous antigen and said amino acid sequence assemble as a hybrid particle. 
     
     
         2 . The composition of  claim 1 , wherein said heterologous antigen is inserted within an immunodominant loop or within an alpha-helix adjacent to said immunodominant loop of said hepadnavirus core antigen. 
     
     
         3 . The composition of  claim 1 , wherein said heterologous antigen is inserted at a position chosen from N-terminal or C-terminal. 
     
     
         4 . The composition of  claim 1 , wherein said heterologous antigen comprises at least one B cell epitope. 
     
     
         5 . The composition of  claim 1 , wherein said heterologous antigen comprises at least one T helper cell epitope. 
     
     
         6 . The composition of  claim 1 , wherein C-terminal sequence of the hepadnavirus core antigen is replaced by from 1 to 100 amino acids. 
     
     
         7 . The composition of  claim 6 , wherein said 1 to 100 amino acids does not consist of cysteine or of wild type C-terminal sequence of said hepadnavirus core antigen. 
     
     
         8 . The composition of  claim 1 , wherein said hepadnavirus core antigen is selected from the group consisting of a rodent hepadnavirus core antigen, an avihepadnavirus core antigen, and a primate hepadnavirus core antigen. 
     
     
         9 . The composition of  claim 8 , wherein said rodent hepadnavirus core antigen is selected from the group consisting of wherein a woodchuck hepadnavirus core antigen, a ground squirrel hepadnavirus core antigen, and an arctic ground squirrel hepadnavirus core antigen. 
     
     
         10 . The composition of  claim 8 , wherein said avihepadnavirus core antigen is selected from the group consisting of a duck hepadnavirus core antigen, a Ross' goose hepadnavirus core antigen, a hereon hepadnavirus core antigen, a Sheldgoose hepadnavirus core antigen, and a stork hepadnavirus core antigen. 
     
     
         11 . The composition of  claim 8 , wherein said primate hepadnavirus core antigen is selected from the group consisting of a human hepatitis B virus core antigen and a nonhuman primate hepadnavirus core antigen. 
     
     
         12 . The composition of  claim 11 , wherein said nonhuman primate hepadnavirus core antigen is selected from the group consisting of a chimpanzee hepatitis B virus core antigen, a gibbon hepatitis B virus core antigen, an orangutan hepatitis virus core antigen, and a woolly monkey hepatitis virus core antigen. 
     
     
         13 . The composition of  claim 1 , wherein said amino acid sequence further comprises at least one immune enhancer sequence. 
     
     
         14 . The composition of  claim 1 , wherein said heterologous antigen further comprises flanking glutamic acid residues. 
     
     
         15 . The composition of  claim 1 , wherein said heterologous antigen further comprises flanking aspartic acid residues. 
     
     
         16 . A vaccine comprising the antigenic composition of  claim 1  and an adjuvant. 
     
     
         17 . The vaccine of  claim 16 , formulated for human administration. 
     
     
         18 . A nucleic acid sequence encoding a hybrid hepadnavirus core antigen comprising a heterologous antigen inserted within the amino acid sequence of a hepadnavirus core antigen, wherein said heterologous antigen is 50 or fewer amino acids in length, and wherein said heterologous antigen and said amino acid sequence assemble as a hybrid particle. 
     
     
         19 . An expression vector comprising the nucleic acid sequence of  claim 18 . 
     
     
         20 . A host cell comprising the expression vector of  claim 19 .