Compositions and methods for the treatment or prevention of hepatitis B virus infection
Disclosed are yeast-based immunotherapeutic compositions, hepatitis B virus (HBV) antigens, and fusion proteins for the treatment and/or prevention of HBV infection and symptoms thereof, as well as methods of using the yeast-based immunotherapeutic compositions, HBV antigens, and fusion proteins for the prophylactic and/or therapeutic treatment of HBV and/or symptoms thereof.
1. An immunotherapeutic composition comprising:
a) a yeast vehicle; and
b) a fusion protein comprising HBV antigens, wherein the HBV antigens consist of:
i) an HBV X antigen having an amino acid sequence that is at least 95% identical to positions 1-60 of SEQ ID NO:130;
ii) an HBV surface antigen having an amino acid sequence that is at least 95% identical to positions 63-461 of SEQ ID NO:130; and
iii) an HBV core antigen having an amino acid sequence that is at least 95% identical to positions 462 to 643 of SEQ ID NO:130;
wherein the composition elicits an HBV-specific immune response and wherein the fusion protein is expressed by the yeast vehicle.
2. The immunotherapeutic composition of claim 1 , wherein the amino acid sequence of HBV X antigen consists of positions 1-60 of SEQ ID NO:130.
3. The immunotherapeutic composition of claim 1 , wherein the amino acid sequence of the HBV surface antigen consists of positions 63-461 of SEQ ID NO:130.
4. The immunotherapeutic composition of claim 1 , wherein the amino acid sequence of the HBV core antigen consists of positions 462 to 643 of SEQ ID NO:130.
5. The immunotherapeutic composition of claim 1 , wherein the HBV antigens are arranged in the following order, from N- to C-terminus, in the fusion protein: HBV X antigen, HBV surface antigen, HBV core antigen.
6. The immunotherapeutic composition of claim 1 , wherein the fusion protein comprises an amino acid sequence of SEQ ID NO:130 or SEQ ID NO:150.
7. The immunotherapeutic composition of claim 1 , wherein the yeast vehicle is a whole yeast.
8. The immunotherapeutic composition of claim 7 , wherein the whole yeast is heat-inactivated.
9. The immunotherapeutic composition of claim 1 , wherein the yeast vehicle is from Saccharomyces cerevisiae.
10. The immunotherapeutic composition of claim 1 , comprising a pharmaceutically acceptable excipient.
11. The immunotherapeutic composition of claim 1 , wherein the immunotherapeutic composition contains greater than 90% yeast protein and is formulated for administration by injection of a patient.
12. An immunotherapeutic composition comprising:
a) a whole, heat-inactivated yeast from Saccharomyces cerevisiae ; and
b) an HBV fusion protein expressed by the yeast, wherein the fusion protein comprises SEQ ID NO:130.
13. An immunotherapeutic composition comprising:
a) a whole, heat-inactivated yeast from Saccharomyces cerevisiae ; and
b) an HBV fusion protein expressed by the yeast, wherein the fusion protein comprises SEQ ID NO:150.
14. A yeast expressing a fusion protein comprising HBV antigens, wherein the HBV antigens consist of:
a) an HBV X antigen having an amino acid sequence that is at least 95% identical to positions 1-60 of SEQ ID NO:130;
b) an HBV surface antigen having an amino acid sequence that is at least 95% identical to positions 63-461 of SEQ ID NO:130; and
c) an HBV core antigen having an amino acid sequence that is at least 95% identical to positions 462 to 643 of SEQ ID NO:130.
15. A fusion protein comprising HBV antigens, wherein the fusion protein comprises an amino acid sequence that is at least 95% identical to an amino acid sequence of SEQ ID NO:130 or SEQ ID NO:150.
16. The immunotherapeutic composition of claim 1 , wherein the HBV antigens consist of an amino acid sequence that is at least 95% identical to SEQ ID NO:130.
17. The immunotherapeutic composition of claim 1 , wherein the HBV antigens consist of an amino acid sequence of SEQ ID NO:130.
18. The immunotherapeutic composition of claim 7 , wherein the whole yeast is killed.
19. The immunotherapeutic composition of claim 8 , wherein the whole yeast has been lyophilized.
20. The immunotherapeutic composition of claim 7 , wherein the whole yeast is from Saccharomyces cerevisiae.
21. The yeast of claim 14 , wherein the amino acid sequence of HBV X antigen consists of positions 1-60 of SEQ ID NO:130.
22. The yeast of claim 14 , wherein the amino acid sequence of the HBV surface antigen consists of positions 63-461 of SEQ ID NO:130.
23. The yeast of claim 14 , wherein the amino acid sequence of the HBV core antigen consists of positions 462 to 643 of SEQ ID NO:130.
24. The yeast of claim 14 , wherein the HBV antigens consist of an amino acid sequence that is at least 95% identical to SEQ ID NO:130.
25. The yeast of claim 14 , wherein the HBV antigens consist of an amino acid sequence of SEQ ID NO:130.
26. The yeast of claim 14 , wherein the fusion protein comprises an amino acid sequence of SEQ ID NO:150.
27. The yeast of claim 14 , wherein the yeast is from Saccharomyces cerevisiae.
28. A fusion protein comprising HBV antigens, wherein the fusion protein comprises an amino acid sequence of SEQ ID NO:130 or SEQ ID NO:150.