Immunogenic polypeptides comprising a scaffold polypeptide and a L2 polypeptide or a fragment thereof
The present invention relates to an immunogenic polypeptide comprising a) a scaffold polypeptide, and b) a L2 polypeptide or a fragment of said L2 polypeptide, wherein said scaffold polypeptide constrains the structure of said L2 polypeptide, or of a fragment of said L2 polypeptide. Moreover, the present invention relates to a vaccine comprising said immunogenic polypeptide. The present invention is also concerned with a method for producing an antibody against human papillomavirus. Also encompassed by the present invention is an antibody obtained by carrying out the said method.
1. An immunogenic fusion polypeptide comprising:
(a) a scaffold polypeptide selected from the group consisting of thioredoxin polypeptides, and thioredoxin polypeptides from thermophile bacteria; and
(b) a L2 peptide as set forth in one of SEQ ID NOs: 1-15, 20-22 and 31-479, wherein the scaffold polypeptide constrains the structure of the L2 peptide.
2. The immunogenic fusion polypeptide of claim 1 , wherein the scaffold polypeptide is a thioredoxin polypeptide selected from the group consisting of:
(a) a polypeptide as set forth in one of SEQ ID No: 24, SEQ ID No: 25, SEQ ID No: 26, SEQ ID No: 27, Of and SEQ ID No: 28; and
(b) a variant polypeptide that is at least 70% identical to one of the sequences set forth in SEQ ID No: 24, SEQ ID No: 25, SEQ ID No: 26, SEQ ID No: 27, and SEQ ID No: 28.
3. The immunogenic fusion polypeptide according to claim 1 , wherein the L2 peptide is selected from the group consisting of SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 31 and 32.
4. The immunogenic fusion polypeptide according to claim 1 , wherein the L2 peptide has the sequence as shown in SEQ ID NO:2.
5. The immunogenic fusion polypeptide according to claim 1 , wherein the immunogenic polypeptide comprises a multimer of the L2 peptide.
6. The immunogenic fusion polypeptide according to claim 1 , wherein the immunogenic polypeptide has the sequence shown in SEQ ID NO: 29 or 30.
7. A vaccine comprising the immunogenic fusion polypeptide according to claim 1 .
8. A method of immunizing a subject against infection with human papillomavirus (HPV) comprising administering a vaccine comprising the immunogenic fusion polypeptide of claim 1 .
9. A method for producing an antibody against the immunogenic fusion polypeptide of claim 1 , comprising the steps:
(a) providing the immunogenic fusion polypeptide;
(b) immunizing a host with the immunogenic fusion polypeptide; and
(c) harvesting the resulting antibody against the immunogenic fusion polypeptide.
10. The method of claim 9 , wherein the antibody is against human papillomavirus (HPV) genotypes 52, 2, 27, 57 and/or 11.
11. The method of claim 9 , wherein the antibody is polyclonal or monoclonal.
12. The immunogenic fusion polypeptide of claim 1 , wherein:
(a) the scaffold polypeptide is selected from the group consisting of SEQ ID Nos: 24, 25, 26, 27, 28, and 493-496; and
(b) the L2 peptide is selected from the group consisting of SEQ ID Nos: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 31 and 32.
13. The immunogenic fusion polypeptide of claim 1 , wherein the L2 peptide is inserted within the sequence of a thioredoxin polypeptide.
14. An immunogenic fusion polypeptide comprising:
(a) a scaffold polypeptide which is a thioredoxin polypeptide;
(b) an L2 peptide as set forth in one of SEQ ID NOs: 1-15, 20-22 and 31-479, wherein the scaffold polypeptide constrains the structure of the L2 peptide; and
wherein the thioredoxin polypeptide comprises a display site having the sequence of CGPC (SEQ ID NO: 23), and wherein the L2 peptide is inserted between (a) C and G of the display site, (b) G and P of the display site, or (c) P and C of the display site.
15. The immunogenic fusion polypeptide of claim 1 , wherein the immunogenic polypeptide comprises more than one L2 peptides having the same sequence or at least 70% sequence identity.
16. An immunogenic fusion polypeptide comprising:
(a) a scaffold polypeptide which is a thioredoxin polypeptide from a thermophile bacterium; and
(b) an L2 peptide as set forth in one of SEQ ID NOs: 1-15, 20-22 and 31-479, wherein the scaffold polypeptide constrains the structure of the L2 peptide.