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1. WO2012174220 - YEAST-BASED COMPOSITIONS AND METHODS FOR THE TREATMENT OR PREVENTION OF HEPATITIS DELTA VIRUS INFECTION

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What is claimed is:

1. An immunotherapeutic composition comprising:

a) a yeast vehicle; and

b) a fusion protein comprising HDV antigens, wherein the HDV antigens consist of at least one immunogenic domain of an HDV large antigen (HDAg-L) or HDV small antigen (HDAg-S), wherein the nuclear localization sequence (NLS) has been inactivated by substitution or deletion of one or more amino acids of the NLS;

wherein the composition elicits an HDV-specific immune response when administered to a subject.

2. The immunotherapeutic composition of Claim 1, wherein the HDV antigen consists of at least one full-length HDAg-L, except that the nuclear localization sequence (NLS) of the HDAg-L has been inactivated by substitution or deletion of one or more amino acids of the NLS.

3. The immunotherapeutic composition of Claim 2, wherein the NLS is deleted.

4. The immunotherapeutic composition of Claim 1, wherein the HDV antigen consists of a fusion of two or more full-length HDAg-L, except that the nuclear localization sequence (NLS) of each of the HDAg-L has been inactivated by substitution or deletion of one or more amino acids of the NLS.

5. The immunotherapeutic composition of Claim 4, wherein the NLS is deleted.

6. The immunotherapeutic composition of Claim 4, wherein each of the HDAg-L is from a different HDV genotype.

7. The immunotherapeutic composition of Claim 1, wherein the HDV antigen consists of a fusion of three full-length HDAg-L, except that the nuclear localization sequence (NLS) of each of the HDAg-L has been inactivated by substitution or deletion of one or more amino acids of the NLS, wherein each of the HDAg-L is from a different HDV genotype.

8. The immunotherapeutic composition of Claim 1, wherein the HDV antigen comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from SEQ ID NO:34, SEQ ID NO:28, or a corresponding amino acid sequence from another HDV strain.

9. The immunotherapeutic composition of Claim 1, wherein the HDV antigen comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from SEQ ID NO:34, SEQ ID NO:28, or a corresponding amino acid sequence from another HDV strain.

10. The immunotherapeutic composition of Claim 1, wherein the HDV antigen is selected from SEQ ID NO:34, SEQ ID NO:28, or a corresponding sequence from another HDV strain.

11. The immunotherapeutic composition of Claim 1 , wherein the HDAg-L has an amino acid sequence selected from SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, or a corresponding amino acid sequence from another HDV strain.

12. The immunotherapeutic composition of Claim 1, wherein the HDAg-S has an amino acid sequence selected from SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:9, or a corresponding sequence from another HDV strain.

13. The immunotherapeutic composition of Claim 1, wherein the HDV antigen comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, or a corresponding amino acid sequence from another HDV strain.

14. The immunotherapeutic composition of Claim 1, wherein the fusion protein has an amino acid sequence selected from SEQ ID NO:36 or SEQ ID NO:30 or an amino acid sequence that is at least 95% identical to SEQ ID NO:36 or SEQ ID NO:30, respectively.

15. An immunotherapeutic composition comprising:

a) a yeast vehicle; and

b) a fusion protein comprising HDV antigens, wherein the HDV antigens consist of at least one immunogenic domain of an HDV large antigen (HDAg-L) or HDV small antigen (HDAg-S), wherein the HDV antigen is less than a full-length HDAg-L or HDAg-S protein;

wherein the composition elicits an HDV-specific immune response when administered to a subject.

16. The immunotherapeutic composition of Claim 15, wherein the HDV antigen consists of a fusion of at least two or more HDAg-L or HDAg-S proteins, wherein at least one of the HDAg-L or HDAg-S proteins is less than a full-length HDAg-L or HDAg-S protein.

17. The immunotherapeutic composition of Claim 16, wherein each of the HDAg-L or HDAg-S proteins is from a different HDV genotype.

18. The immunotherapeutic composition of Claim 15, wherein the HDV antigen comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from SEQ ID NO: 10, SEQ ID NO: 16, or a corresponding amino acid sequence from another HDV strain.

19. The immunotherapeutic composition of Claim 15, wherein the HDV antigen comprises an amino acid sequence that is at least 97% identical to an amino acid sequence selected from SEQ ID NO: 10, SEQ ID NO: 16, or a corresponding amino acid sequence from another HDV strain.

20. The immunotherapeutic composition of Claim 15, wherein the HDV antigen is selected from SEQ ID NO: 10, SEQ ID NO: 16, or a corresponding sequence from another HDV strain.

21. The immunotherapeutic composition of Claim 15, wherein the HDAg-L has an amino acid sequence selected from SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, or a corresponding amino acid sequence from another HDV strain.

22. The immunotherapeutic composition of Claim 15, wherein the HDAg-S has an amino acid sequence selected from SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:9, or a corresponding sequence from another HDV strain.

23. The immunotherapeutic composition of Claim 1, wherein the fusion protein is selected from SEQ ID NO : 12, SEQ ID NO : 15 , SEQ ID NO : 17, or SEQ ID NO : 18.

24. The immunotherapeutic composition of any preceding claim, wherein the HDV antigen is expressed by the yeast vehicle.

25. The immunotherapeutic composition of any preceding claim, wherein the yeast vehicle is a whole yeast.

26. The immunotherapeutic composition of Claim 25, wherein the whole yeast is killed.

27. The immunotherapeutic composition of Claim 25, wherein the whole yeast is heat-inactivated.

28. The immunotherapeutic composition of any preceding claim, wherein the yeast vehicle is from a yeast genus selected from the group consisting of: Saccharomyces, Candida, Cryptococcus, Hansenula, Kluyveromyces, Pichia, Rhodotorula, Schizosaccharomyces and Yarrowia.

29. The immunotherapeutic composition of any preceding claim, wherein the yeast vehicle is from Saccharomyces .

30. The immunotherapeutic composition of any preceding claim, wherein the yeast vehicle is from Saccharomyces cerevisiae.

31. The immunotherapeutic composition of any preceding claim, wherein the composition is formulated in a pharmaceutically acceptable excipient suitable for administration to a subject.

32. The immunotherapeutic composition of any preceding claim, wherein the composition contains greater than 90% yeast protein.

33. A method to treat hepatitis D virus (HDV) infection or at least one symptom resulting from HDV infection in a subject or improve survival of a subject who is infected with HDV, comprising administering to a subject that has been infected with HDV at least one composition according to any of the preceding claims, wherein administration of the composition to the subject reduces HDV infection or at least one symptom resulting from HDV infection in a subject.

34. The method of Claim 33, further comprising administering to the subject one or more additional agents useful for treating or ameliorating a symptom of HDV infection.

35. The method of Claim 34, wherein the compound is an interferon.

36. The method of Claim 24, wherein the interferon is interferon-a.

37. The method of Claim 24, wherein the interferon is pegylated interferon-a2a.

38. The method of Claim 24, wherein the interferon is interferon-λ.

39. The method of Claim 33, wherein the subject is chronically infected with hepatitis B virus (HBV).

40. The method of Claim 39, further comprising administering to the subject an anti-viral compound to treat the HBV infection.

41. The method of Claim 40, wherein the anti-viral compound is selected from the group consisting of: tenofovir, lamivudine, adefovir, telbivudine, entecavir, and combinations thereof.

42. A method to elicit an antigen- specific, cell-mediated immune response against an HDV antigen, comprising administering to a subject at least one composition according to any one of Claims 1 to 32.

43. A method to prevent HDV infection in a subject, comprising administering to a subject that has not been infected with HDV, at least one composition according to any one of Claims 1 to 32.

44. The method of Claim 43, wherein the subject is chronically infected with hepatitis B virus (HBV).

45. The method of Claim 44, further comprising administering to the subject an anti-viral compound to treat the HBV infection.

46. A method to immunize a population of individuals against HDV, comprising administering to the population of individuals at least one composition according to any one of Claims 1 to 32.

47. The method of Claim 46, wherein the population of individuals is chronically infected with HBV.

48. The composition of any one of Claims 1 to 32, for use to treat HDV infection.

49. The composition of any one of Claims 1 to 32, for use to prevent HDV infection in a subject.

50. The composition of Claim 49, wherein the subject is chronically infected with HBV.

51. Use of the composition of any one of Claims 1 to 32 in the preparation of a medicament to treat HDV infection.

52. Use of the composition of any one of Claims 1 to 32 in the preparation of a medicament to prevent HDV infection.