Multimeric multiepitope influenza vaccines

1. An isolated polynucleotide encoding an influenza multi-epitope polypeptide, wherein the multi-epitope polypeptide comprises multiple copies of a plurality of influenza virus peptide epitopes wherein the polypeptide consists of:

i. B(X 1 ZX 2 Z . . . X m ) n B; or

ii. B(X 1 ) n Z(X 2 ) n Z . . . (X m ) n B;

wherein B is an optional sequence of 1-4 amino acid residues; n is at each occurrence independently an integer of 2-50; m is 3-15; each of X 1 , X 2 . . . X m is an influenza peptide epitope selected from the group consisting of: HA 354-372 (E1, SEQ ID NO: 82), HA 91-108 (E2, SEQ ID NO: 48), M1 2-12 (E3, SEQ ID NO: 25), HA 150-159 (E4, SEQ ID NO: 52), HA 143-149 (E5, SEQ ID NO: 51), NP 206-229 (E6, SEQ ID NO: 64), HA 307-319 (E7, SEQ ID NO: 59), NP 335-350 (E8, SEQ ID NO: 69), and NP 380-393 (E9, SEQ ID NO: 70); and Z at each occurrence is a bond or a spacer of 1-4 amino acid residues.

2. An isolated polynucleotide encoding a polypeptide sequence selected from the group consisting of:

i. nine different influenza virus peptide epitopes arranged in the following alternating sequential polymeric structure [E1E2E3E4E5E6E7E8E9] n , wherein n is 3-6;

ii. 3-6 repeats of nine different influenza virus peptide epitopes arranged in the following block copolymer structure [E1E1E1-E2E2E2-E3E3E3-E4E4E4-E5E5E5-E6E6E6-E7E7E7-E8E8E8-E9E9E9];

iii. 4-6 repeats of five different B-cell type influenza virus peptide epitopes arranged in the following alternating sequential polymeric structure [E1E2E3E4E5] 6 ,

iv. 4-6 repeats of four different T-cell type influenza virus peptide epitopes arranged in the following alternating sequential polymeric structure [E7E8E9E6] 6 ;

wherein E1 is HA 354-372 (SEQ ID NO:82), E2 is HA 91-108 (SEQ ID NO:48), E3 is M1 2-12 (SEQ ID NO:25), E4 is HA 150-159 (SEQ ID NO:52), E5 is HA 143-149 (SEQ ID NO:51), E6 is NP 206-229 (SEQ ID NO:64), E7 is HA 307-319 (SEQ ID NO:59), E8 is NP 335-350 (SEQ ID NO:69), and E9 is NP 380-393 (SEQ ID NO:70).

3. The isolated polynucleotide according to claim 2 encoding the polypeptide comprising the three repeats of the nine different influenza virus peptide epitopes arranged in the following block copolymer structure [E1E1E1-E2E2E2-E3E3E3-E4E4E4-E5E5E5-E6E6E6-E7E7E7-E8E8E8-E9E9E9].

4. The isolated polynucleotide according to claim 2 comprising a nucleotide sequence selected from the group consisting of the nucleotides of SEQ ID NO:83, SEQ ID NO:85 and SEQ ID NO:87.

5. The isolated polynucleotide according to claim 2 encoding a polypeptide sequence selected from the group consisting of the amino acids of SEQ ID NO:84, SEQ ID NO:86 and SEQ ID NO:88.

6. An isolated polynucleotide encoding an influenza multi-epitope polypeptide, wherein the multi-epitope polypeptide comprises 2-50 copies of 4 to 9 influenza virus peptide epitopes selected from the group consisting of: HA 354-372 (E1, SEQ ID NO: 82), HA 91-108 (E2, SEQ ID NO: 48), M1 2-12 (E3, SEQ ID NO: 25), HA 150-159 (E4, SEQ ID NO: 52), HA 143-149 (E5, SEQ ID NO: 51), NP 206-229 (E6, SEQ ID NO: 64), HA 307-319 (E7, SEQ ID NO: 59), NP 335-350 (E8, SEQ ID NO: 69), and NP 380-393 (E9, SEQ ID NO: 70).

7. The isolated polynucleotide according to claim 6 encoding a polypeptide comprising 2-50 copies of the nine influenza peptide epitopes consisting of: HA 354-372 (E1, SEQ ID NO: 82), HA 91-108 (E2, SEQ ID NO: 48), M1 2-12 (E3, SEQ ID NO: 25), HA 150-159 (E4, SEQ ID NO: 52), HA 143-149 (E5, SEQ ID NO: 51), NP 206-229 (E6, SEQ ID NO: 64), HA 307-319 (E7, SEQ ID NO: 59), NP 335-350 (E8, SEQ ID NO: 69), and NP 380-393 (E9, SEQ ID NO: 70).