Compositions and Methods

Abstract

The invention relates to a composition suitable for inducing a T cell mediated immune response against an influenza virus in a vertebrate, said composition comprising nucleic acid encoding one or more epitopes of one or more internal proteins of influenza virus, wherein said composition comprises nucleic acid encoding at least two said epitopes, at least one epitope being from each of two or more internal proteins of influenza virus. The invention also relates to uses of same and to methods involving same.

1 . A composition suitable for inducing a T cell mediated immune response against an influenza virus in a vertebrate, said composition comprising nucleic acid encoding one or more epitopes of one or more internal proteins of influenza virus, wherein said composition comprises nucleic acid encoding at least two said epitopes, at least one epitope being from each of two or more internal proteins of influenza virus. 
     
     
         2 . A composition according to  claim 1  wherein said internal proteins comprise nucleoprotein and matrix 1 protein. 
     
     
         3 . A composition according to  claim 2  wherein said epitopes are provided in the form of a nucleoprotein-matrix 1 protein fusion. 
     
     
         4 . A composition according to  claim 3  wherein said proteins are arranged in the order N terminus-nucleoprotein-matrix1 protein-C terminus. 
     
     
         5 . A composition according to  claim 4  wherein said nucleoprotein and matrix 1 proteins are separated by a linker sequence. 
     
     
         6 . A composition according to  claim 5  wherein said linker sequence has the amino acid sequence GGGPGGG. 
     
     
         7 . A composition according to  claim 1  wherein said internal proteins are from the H3N2 influenza strain. 
     
     
         8 . A composition according to  claim 7  wherein said internal proteins are from the H3N2 influenza strain subtype A/Panama/2007/99. 
     
     
         9 . A composition according to  claim 1  wherein the coding sequence of the nucleic acid sequence encoding said internal proteins and/or linker polypeptides has been codon optimised for human codon usage. 
     
     
         10 . A composition according to  claim 1  wherein said epitopes are provided in the form of a polypeptide comprising the amino acid sequence of SEQ ID NO:1. 
     
     
         11 . A composition according to  claim 1  wherein said epitopes are encoded by a nucleic acid comprising the nucleotide sequence of SEQ ID NO:2. 
     
     
         12 . A composition according to  claim 1  wherein said coding sequence is present in an adenovirus based vector. 
     
     
         13 . A composition according to  claim 1  wherein said coding sequence is present in a MVA based vector. 
     
     
         14 . A composition according to  claim 1  wherein said coding sequence is present in an avipox or orthopox based vector. 
     
     
         15 . A composition according to  claim 1  further comprising adjuvant. 
     
     
         16 . A composition according to  claim 1  which induces T cell responses to both the NP and M1 antigens. 
     
     
         17 . A method of inducing a T-cell mediated immune response against an influenza virus in a subject comprising administering to said subject a composition comprising nucleic acid encoding one or more epitopes of one or more internal proteins of influenza virus, wherein said composition comprises nucleic acid encoding at least two said epitopes, at least one epitope being from each of two or more internal proteins of influenza virus said composition optionally further comprising an adjuvant. 
     
     
         18 - 19 . (canceled) 
     
     
         20 . The method of  claim 17 , wherein administration of said compositions which induces T cell responses to both the NP and M1 antigens. 
     
     
         21 . The method of  claim 17 , wherein said epitopes are encoded in the form of a nucleoprotein-matrix 1 protein fusion, wherein said nucleoprotein and matrix 1 protein components of said fusion are optionally separated by a linker. 
     
     
         22 . The method of  claim 17 , wherein said internal proteins are from the H3N2 influenza strain.