HPV vaccines
The present invention relates to novel vaccines against Human papillomavirus (HPV) infections, based on recombinant capsid-display adenovirus vectors. Described are capsid modified replication deficient adenovirus particles encoding and displaying multiple HPV L2 antigenic fragments, via a minor capsid protein IX, and their use for eliciting an immune response in order to provide protection against infections from multiple HPV types.
1. A recombinant adenoviral vector encoding a polypeptide comprising a capsid protein IX fused to an antigen, wherein said antigen comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7.
2. The recombinant adenoviral vector according to claim 1 , wherein the antigen comprises the amino acid sequence of SEQ ID NO: 3.
3. The recombinant adenoviral vector according to claim 1 , wherein the antigen comprises the amino acid sequence of SEQ ID NO: 5.
4. The recombinant adenoviral vector according to claim 1 , wherein said antigen comprises the amino acid sequence of SEQ ID NO: 6.
5. The recombinant adenoviral vector according to claim 1 wherein said antigen comprises the amino acid sequence of SEQ ID NO:1.
6. The recombinant adenoviral vector according claim 1 , wherein said antigen comprises SEQ ID NO: 7.
7. The recombinant adenoviral vector according to claim 1 , wherein said antigen comprises the amino acid sequence of SEQ ID NO: 2.
8. The recombinant adenoviral vector according to claim 1 , wherein said antigen comprises the amino acid sequence of SEQ ID NO:4.
9. A recombinant adenoviral vector encoding a polypeptide comprising a capsid protein IX fused to an antigen, wherein said antigen comprises 4 consecutive amino acid motifs of about 20 to about 40 amino acids, wherein the first motif comprises the amino acid residues 17-36 of a HPV L2 protein of the HPV type 31, the second motif comprises the amino acid residues 69-81 of a HPV L2 protein of the HPV type 45, the third motif comprises the amino acid residues 108-121 of a HPV L2 protein of the HPV type 18, and the fourth motif comprises the amino acid residues 108-121 of a HPV L2 protein of the HPV type 16.
10. The recombinant adenoviral vector according to claim 9 , wherein said antigen comprises the amino acid sequence of SEQ ID NO:8.
11. The recombinant adenoviral vector according to claim 1 , wherein the protein IX and the antigen are linked together by a linker or a spacer.
12. The recombinant adenoviral vector according to claim 11 , wherein the linker comprises an amino acid sequence having 3 consecutive flexible residues of glycine.
13. The recombinant adenoviral vector according to claim 1 , wherein said vector is selected from the group consisting of: HAdV4, HAdV11, HAdV26, HAdV35, HAdV48, HAdV49, HAdV50, non-human primate vectors and chimeric vectors.
14. The recombinant adenoviral vector according to claim 11 , wherein said adenoviral vector is a HAdV26 or HAdV35.
15. The recombinant adenoviral vector according to claim 1 , wherein said vector further comprises a nucleic acid encoding one or more heterologous proteins as a transgene.
16. A composition comprising a combination of at least two different recombinant adenoviral vectors according to claim 1 .
17. A composition comprising two recombinant adenoviral vectors according to claim 1 , wherein the antigen of said first vector comprises the amino acid sequence of SEQ ID NO:6 and the antigen of said second vector comprises the amino acid sequence of SEQ ID NO:7.
18. A vaccine comprising a recombinant adenoviral vector according to claim 1 , further comprising a pharmaceutically acceptable excipient.
19. A method of inducing an immune response in a subject, comprising administering the vaccine of claim 18 to said subject.
20. The recombinant adenoviral vector according to claim 9 , wherein the protein IX and the antigen are linked together by a linker or a spacer.
21. The recombinant adenoviral vector according to claim 20 , wherein the linker comprises an amino acid sequence having 3 consecutive flexible residues of glycine.
22. The recombinant adenoviral vector according to claim 9 , wherein said vector is selected from the group consisting of: HAdV4, HAdV11, HAdV26, HAdV35, HAdV48, HAdV49, HAdV50, non-human primate vectors and chimeric vectors.
23. The recombinant adenoviral vector according to claim 9 , wherein said vector further comprises a nucleic acid encoding one or more heterologous proteins as a transgene.
24. A vaccine comprising a recombinant adenoviral vector according to claim 9 , further comprising a pharmaceutically acceptable excipient.
25. A method of inducing an immune response in a subject, comprising administering the vaccine of claim 24 to said subject.