Composition for treating HBV infection
The present invention provides a composition comprising hepatitis B virus (HBV) component(s), and which may be either nucleic acid- or polypeptide-based as well as nucleic acid molecules and vectors encoding such HBV component(s). It also relates to infectious viral particles and host cells comprising such nucleic acid molecules or vectors. It also provides composition and kits of parts comprising such nucleic acid molecules, vectors, infectious viral particles or host cells and the therapeutic use thereof for preventing or treating HBV infections.
1. A kit of parts for use in the treatment of an HBV infection, wherein said kit comprises:
a first vector which is an E1-defective Ad vector comprising inserted in place of the E1 region a nucleic acid molecule placed under the control of the CMV promoter and encoding a polymerase moiety comprising an amino acid sequence as shown in SEQ ID NO:7, SEQ ID NO:8, or SEQ ID NO:9 or in SEQ ID NO:7 with the substitution of the Asp residue in position 494 to an His residue and the substitution of the Glu residue in position 672 to an His residue; and
a second vector which is an E1-defective Ad vector comprising inserted in place of the E1 region a nucleic acid molecule placed under the control of the CMV promoter and encoding a core moiety and an env moiety comprising an amino acid sequence as shown in SEQ ID NO:20 or the portion of SEQ ID NO:20 starting at residue 1 and ending at residue 251 or the portion of SEQ ID NO:20 starting at residue 1 and ending at residue 221.
2. The kit of parts according to claim 1 further comprising a third vector expressing an immunomodulator.
3. An infectious viral particle comprising the first vector and the second vector according to claim 1 .
4. A composition comprising the first vector and the second vector according to claim 1 and a pharmaceutically acceptable vehicle.
5. The composition according to claim 4 , which further comprises one or more adjuvant(s) suitable for systemic or mucosal application in humans.
6. The composition according to claim 5 , which is formulated for intramuscular or subcutaneous administration.
7. A composition comprising the infectious viral particle according to claim 3 and a pharmaceutically acceptable vehicle.
8. The composition according to claim 7 , which further comprises one or more adjuvant(s) suitable for systemic or mucosal application in humans.
9. The composition according to claim 7 , which is formulated for intramuscular or subcutaneous administration.
10. The composition according to claim 8 , which is formulated for intramuscular or subcutaneous administration.
11. The composition according to claim 7 , which comprises from about 10 5 to about 10 13 infection units of an infectious viral particle.
12. The composition according to claim 8 , which comprises from about 10 5 to about 10 13 infection units of an infectious viral particle.
13. The composition according to claim 9 , which comprises from about 10 5 to about 10 13 infection units of an infectious viral particle.
14. The composition according to claim 10 , which comprises from about 10 5 to about 10 13 infection units of an infectious viral particle.
15. The composition according to claim 4 , which is formulated for intramuscular or subcutaneous administration.
16. The composition according to claim 5 , claim 6 , or claim 15 , which comprises from about 10 5 to about 10 13 infection units of a viral vector.
17. The composition according to claim 4 , which comprises from about 10 5 to about 10 13 infection units of a viral vector.
18. A kit of parts for use in the treatment of an HBV infection, wherein said kit comprises a plurality of active agents including the infectious viral particle according to claim 3 .
19. A kit of parts for use in the treatment of an HBV infection, wherein said kit comprises a plurality of active agents including the composition according to claim 4 .
20. A composition comprising the first vector, the second vector, and the third vector according to claim 2 and a pharmaceutical acceptable vehicle.
21. The composition according to claim 20 , which further comprises one or more adjuvant(s) suitable for systemic or mucosal application in humans.
22. The composition according to claim 20 , which is formulated for intramuscular or subcutaneous administration.
23. The composition according to claim 21 , which is formulated for intramuscular or subcutaneous administration.
24. The composition according to claim 20 , claim 21 , claim 22 , or claim 23 which comprises from about 10 5 to about 10 13 infection units of a viral vector.
25. A composition comprising
an infectious viral particle comprising the first vector, the second vector, and the third vector according to claim 2 ; and
a pharmaceutical acceptable vehicle.
26. The composition according to claim 25 , which further comprises one or more adjuvant(s) suitable for systemic or mucosal application in humans.
27. The composition according to claim 25 , which is formulated for intramuscular or subcutaneous administration.
28. The composition according to claim 26 , which is formulated for intramuscular or subcutaneous administration.
29. The composition according to claim 25 , claim 26 , claim 27 , or claim 28 , which comprises from about 10 5 to about 10 13 infection units of a viral vector.
30. A method of inducing or stimulating an immune response, against HBV in a host organism comprising administering to said organism at least one of the infectious viral particle according to claim 3 , or of the composition according to claim 4 , so as to induce or stimulate said immune response.
31. The method according to claim 30 , wherein said method is used in combination with a standard of care comprising cytokines and/or nucleotide or nucleoside analogs selected from the group consisting of lamivudine, entecavir, telbivudine, adefovir, dipivoxil, and tenofovir.
32. The method of inducing or stimulating an immune response according to claim 30 , wherein the immune response is a CD4+ and/or CD8+-mediated cellular response.