Chimpanzee adenovirus vaccine carriers
The present invention provides recombinant replication-defective adenoviral vectors derived from chimpanzee adenoviruses and methods for generating recombinant adenoviruses in human E1-expressing cell lines. The invention also provides compositions and methods suitable for use for the delivery and expression of transgenes encoding immunogens against which a boosted immune response is desired. The invention further provides methods of generating clinical grade vector stocks suitable for use in humans. In a particular embodiment the invention contemplates the use of vectors comprising transgenes which encode tumor associated antigens in vaccines and pharmaceutical compositions for the prevention and treatment of cancer.
1. A recombinant chimpanzee adenoviral vector comprising an adenoviral genome comprising a sequence of nucleotides that encodes the peptide as set forth in SEQ ID NO:116, wherein said adenoviral genome is modified in that at least one gene selected from the group consisting of E1, E2, E3 and E4 is functionally deleted.
2. The recombinant chimpanzee adenoviral vector according to claim 1 , wherein the adenoviral genome comprises a sequence of nucleotides as set forth in SEQ ID NO: 115.
3. The recombinant chimpanzee adenoviral vector according to claim 1 , wherein the vector comprises a complete deletion of its E1 genes and further wherein the vector optionally comprises a complete deletion of its E3 genes.
4. The recombinant chimpanzee adenoviral vector according to claim 1 , wherein the vector further comprises a transgene encoding at least one tumor associated antigen (TAA) operatively linked to a promoter capable of directing expression of the transgene.
5. The recombinant chimpanzee adenoviral vector according to claim 4 , wherein the at least one TAA is selected from the group consisting of: HER2NEU, CEA, EPCAM, PSA, PSMA, TELOMERASE, GP100, MELAN-A/MART-1, MUC-1, NY-ESO-1, SURVIVIN, STROMELYSIN 3, TYROSINASE, MAGE3, CML68, CLM66, OY-TES-1, SSX-2, SART-1, SART-2, SART-3, NY-CO-58, NY-BR-62, HKLP2, 5T4 and VEGFR2.
6. The recombinant chimpanzee adenoviral vector according to claim 1 , wherein the vector further comprises a transgene encoding at least one immunogen operatively linked to regulatory sequences which direct expression of said transgene in mammalian cells.
7. The recombinant chimpanzee adenoviral vector according to claim 6 , wherein the immunogen is derived from an infectious agent selected from the group consisting of HIV, HBV, HCV, HPV, HSV1, HSV2, SARS CoV, Plasmodium malariae , Ebola virus, West Nile virus, Dengue virus, Influenza A, Influenza B, Mycobacterium tuberculosis and Leishmania major.
8. An isolated host cell comprising a recombinant chimpanzee adenoviral vector according to claim 1 .
9. The isolated host cell of claim 8 , wherein the adenoviral genome comprises a sequence of nucleotides as set forth in SEQ ID NO: 115.
10. The isolated host cell of claim 8 , wherein the host cell is a 293 cell and which propagates the recombinant chimpanzee adenoviral vector.
11. A method of boosting an antigen-specific immune response in a mammal comprising administering to said mammal a sufficient amount of the recombinant chimpanzee adenoviral vector according to claim 6 , which expresses at least one antigen, and wherein the mammal was previously exposed at least once with said at least one antigen.
12. The method of claim 11 , wherein the adenoviral genome comprises a sequence of nucleotides as set forth in SEQ ID NO: 115.
13. The method of claim 11 , wherein the vector comprises a complete deletion of its E1 genes and further wherein the vector optionally comprises a deletion of its E3 genes.
14. The method of claim 11 , wherein the boosted immune response comprises the production of antigen-specific CD8+ T cells.
15. The method of claim 11 , wherein the immune response is a boosted immune response that is specific for a tumor-associated antigen (TAA).
16. The method of claim 15 , wherein the TAA is selected from the group consisting of: HER2NEU, CEA, EPCAM, PSA, PSMA, TELOMERASE, GP100, MELAN-A/MART-1, MUC-1, NY-ESO-1, SURVIVIN, STROMELYSIN 3, TYROSINASE, MAGE3, CML68, CLM66, OY-TES-1, SSX-2, SART-1, SART-2, SART-3, NY-CO-58, NY-BR-62, HKLP2, 5T4 and VEGFR2.
17. The method of claim 11 , wherein the antigen is derived from an infectious agent selected from the group consisting of HIV, HBV, HCV, HPV, HSV1, HSV2, SARS CoV, Leishmania major, Plasmodium malariae , Ebola virus, West Nile virus, Dengue virus, Influenza A, Influenza B, and Mycobacterium tuberculosis.
18. A method of eliciting an immune response in a mammal comprising administering to said mammal a sufficient amount of the recombinant chimpanzee adenoviral vector according to claim 6 , wherein the administration of the adenoviral vector elicits an immune response.
19. The method of claim 18 , wherein the adenoviral genome comprises the sequence of nucleotides as set forth in SEQ ID NO: 115.
20. The method of claim 18 , wherein the antigen is derived from an infectious agent selected from the group consisting of HIV, HBV, HCV, HPV, HSV1, HSV2, SARS CoV, Leishmania major, Plasmodium malariae , Ebola virus, West Nile virus, Dengue virus, Influenza A, Influenza B, and Mycobacterium tuberculosis.
21. The method of claim 18 , wherein the antigen is a tumor-associated antigen (TAA).
22. The method of claim 21 , wherein the TAA is selected from the group consisting of: HER2NEU, CEA, EPCAM, PSA, PSMA, TELOMERASE, GP100, MELAN-A/MART-1, MUC-1, NY-ESO-1, SURVIVIN, STROMELYSIN 3, TYROSINASE, MAGE3, CML68, CLM66, OY-TES-1, SSX-2, SART-1, SART-2, SART-3, NY-CO-58, NY-BR-62, HKLP2, 5T4 and VEGFR2.
23. The recombinant chimpanzee adenoviral vector of claim 1 , wherein the adenoviral genome further comprises a sequence of nucleotides that encodes a peptide as set forth in SEQ ID NO: 77.
24. The recombinant chimpanzee adenoviral vector according to claim 2 , wherein the adenoviral genome further comprises a sequence of nucleotides as set forth in SEQ ID NO: 76.
25. The isolated host cell of claim 9 , wherein the adenoviral genome further comprises a sequence of nucleotides as set forth in SEQ ID NO:76.
26. The method of claim 12 , wherein the adenoviral genome further comprises a sequence of nucleotides as set forth in SEQ ID NO: 76.
27. The method of claim 20 , wherein the adenoviral genome further comprises a sequence of nucleotides as set forth in SEQ ID NO: 76.