Compositions and methods for enhancing the immunogenicity of antigens
View Patent ↗The present invention includes compositions, methods and kits for enhancing the immunogenicity of an antigen via fusion to a Listerial protein. The present invention further encompasses Listeria vaccine strains for enhancing the immunogenicity of an antigen.
1. A vector comprising an isolated nucleic acid sequence encoding a fusion protein comprising a truncated ActA protein and a tumor antigen, wherein said nucleic acid sequence encoding said truncated ActA protein consists of nucleic acids 1-1170 that encode the N-terminal first 390 amino acids of a Listeria monocytogenes ActA protein.
2. The vector of claim 1 , wherein said isolated nucleic acid sequence encoding said truncated ActA protein, consists of the sequence set forth in SEQ ID NO: 24.
3. The vector of claim 1 , wherein said Listeria monocytogenes is the 10403s strain.
4. The vector of claim 1 , wherein said truncated ActA protein comprises one or more PEST-containing sequences set forth in SEQ ID No: 2-5.
5. The vector of claim 1 , wherein said tumor antigen is human papilloma virus (HPV) E6, or HPV E7.
6. The vector of claim 1 , wherein said tumor antigen is Her-2/Neu, NY-ESO-1, human telomerase, WT-1, proteinase 3, TRP-2, carcinoembryonic antigen (CEA), or PSA antigen.
7. An isolated nucleic acid encoding a fusion protein comprising a truncated ActA protein and a tumor antigen, wherein said nucleic acid encoding said truncated ActA protein consists of nucleic acids 1-1170 that encode the N-terminal first 390 amino acids of a Listeria monocytogenes ActA protein.
8. The isolated nucleic acid of claim 7 , wherein said nucleic acid encoding said truncated ActA protein consists of the sequence set forth in SEQ ID NO: 24.
9. The isolated nucleic acid of claim 7 , wherein said Listeria monocytogenes is the 10403s strain.
10. The isolated nucleic acid of claim 7 , wherein said truncated ActA protein comprises one or more PEST-containing sequences set forth in SEQ ID No: 2-5.
11. The isolated nucleic acid of claim 7 , wherein said tumor antigen is (HPV) E6, or HPV E7.
12. The isolated nucleic acid of claim 7 , wherein said tumor antigen is Her-2/Neu, NY-ESO-1, human telomerase, WT-1, proteinase 3, TRP-2, carcinoembryonic antigen (CEA), or PSA antigen.
13. A vector comprising an isolated nucleic acid sequence encoding a fusion protein comprising a truncated ActA protein and a tumor antigen, wherein said truncated ActA comprises a PEST-like sequence as set forth in SEQ ID NO: 2; and wherein said isolated nucleic acid sequence encoding said truncated ActA protein consists of nucleic acids 1-1170 that encode the N-terminal first 390 amino acids of a Listeria monocytogenes ActA protein.
14. The vector of claim 13 , wherein said isolated nucleic acid sequence encoding said truncated ActA protein, consists of the sequence set forth in SEQ ID NO: 24.
15. The vector of claim 13 , wherein said Listeria monocytogenes is the 10403s strain.
16. The vector of claim 13 , wherein said truncated ActA protein further comprises one or more PEST-containing sequences as set forth in SEQ ID No: 3-5.
17. The vector of claim 13 , wherein said tumor antigen is (HPV) E6, or HPV E7.
18. The vector of claim 13 , wherein said tumor antigen is Her-2/Neu, NY-ESO-1, human telomerase, WT-1, proteinase 3, TRP-2, carcinoembryonic antigen (CEA), or PSA antigen.
19. An isolated nucleic acid encoding a fusion protein comprising a truncated ActA protein and a tumor antigen, wherein said truncated ActA comprises a PEST-like sequence as set forth in SEQ ID NO: 2; wherein said nucleic acid encoding said truncated ActA protein consists of nucleic acids 1-1170 that encode the N-terminal first 390 amino acids of a Listeria monocytogenes ActA protein.
20. The isolated nucleic acid of claim 19 , wherein said nucleic acid encoding said truncated ActA protein consists of the sequence set forth in SEQ ID NO: 24.
21. The isolated nucleic acid of claim 19 , wherein said Listeria monocytogenes is the 10403s strain.
22. The isolated nucleic acid of claim 19 , wherein said truncated ActA protein further comprises one or more PEST-containing sequences as set forth in SEQ ID No: 3-5.
23. The isolated nucleic acid of claim 19 , wherein said tumor antigen is (HPV) E6, or HPV E7.
24. The isolated nucleic acid of claim 19 , wherein said tumor antigen is Her-2/Neu, NY-ESO-1, human telomerase, WT-1, proteinase 3, TRP-2, carcinoembryonic antigen (CEA), or PSA antigen.
25. A vector comprising an isolated nucleic acid sequence encoding a PEST-like sequence selected from the group consisting of SEQ ID NOs: 2-5 and a nucleic acid sequence encoding a tumor antigen, wherein said nucleic acid sequence encoding a PEST-like sequence and said nucleic acid sequence encoding said tumor antigen is expressed in a cell as a fusion protein.
26. The vector of claim 25 , wherein said tumor antigen is (HPV) E6, or HPV E7.
27. The vector of claim 25 , wherein said tumor antigen is Her-2/Neu, NY-ESO-1, human telomerase, WT-1, proteinase 3, TRP-2, carcinoembryonic antigen (CEA), or PSA antigen.
28. An isolated nucleic acid encoding a fusion protein, wherein said nucleic acid encodes a PEST-like sequence selected from the group consisting of SEQ ID NOs: 2-5 and a tumor antigen, wherein said nucleic acid encoding said PEST-like sequence and said tumor antigen is expressed in a cell.
29. The isolated nucleic acid of claim 28 , wherein said tumor antigen is (HPV) E6, or HPV E7.
30. The isolated nucleic acid of claim 28 , wherein said tumor antigen is Her-2/neu, NY-ESO-1, human telomerase, WT-1, proteinase 3, TRP-2, carcinoembryonic antigen (CEA), or PSA antigen.