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 Listeria monocytogenes vaccine strain comprising an antigen fused to a truncated ActA protein, wherein said truncated ActA protein consists of amino acids 1-390 of said ActA protein; wherein said truncated ActA protein comprises a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5; and wherein said antigen is selected from the group consisting of human papilloma virus (HPV) E6, HPV E7, Her-2/Neu, NY-ESO-1, human telomerase, WT-1, proteinase 3, TRP-2 and PSA antigen.
2. The Listeria monocytogenes vaccine strain of claim 1 , wherein said truncated ActA protein consists of the sequence set forth in SEQ ID NO: 23.
3. The Listeria monocytogenes vaccine strain of claim 1 , wherein said antigen and said truncated ActA protein are encoded by a vector.
4. The Listeria monocytogenes vaccine strain of claim 1 , wherein said antigen and said truncated ActA protein are expressed from a promoter selected from the group consisting of an hly promoter, a prfA promoter, and a p60 promoter.
5. A kit for eliciting an enhanced immune response to an antigen, the kit comprising (a) the Listeria monocytogenes vaccine strain of claim 1 and (b) a pharmaceutically acceptable carrier, said kit further comprising an applicator, and an instructional material for use thereof.
6. A method of eliciting an enhanced immune response to an antigen, the method comprising administering to a subject an effective amount of a composition comprising a Listeria monocytogenes vaccine strain comprising said antigen fused to a truncated ActA protein, wherein said truncated ActA protein consists of amino acids 1-390 of said ActA protein; and wherein said truncated ActA protein comprises a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5; and wherein said antigen is selected from the group consisting of human papilloma virus (HPV) E6, HPV E7, Her-2/Neu, NY-ESO-1, human telomerase, WT-1, proteinase 3, TRP-2, and PSA antigen.
7. The method of claim 6 , wherein said subject is a human.
8. The method of claim 6 , wherein said composition is suspended in a pharmaceutically acceptable carrier.
9. A Listeria monocytogenes vaccine strain comprising an antigen fused to a PEST-like sequence selected from the group consisting of the sequences set forth in SEQ ID No: 2-5, wherein said antigen is selected from human papilloma virus (HPV) E6, HPV E7, Her-2/Neu, NY-ESO-1, human telomerase, WT-1, proteinase 3, TRP-2, and PSA antigen.
10. The Listeria monocytogenes vaccine strain of claim 9 , wherein said antigen and said PEST-like sequence are encoded by a vector.
11. The Listeria monocytogenes vaccine strain of claim 9 , wherein said antigen and said PEST-like sequence are expressed from a promoter selected from the group consisting of an hly promoter, a prfA promoter, and a p60 promoter.
12. A kit for eliciting an enhanced immune response to an antigen, the kit comprising (a) the Listeria monocytogenes vaccine strain of claim 9 and (b) a pharmaceutically acceptable carrier, said kit further comprising an applicator, and an instructional material for use thereof.
13. A method of eliciting an enhanced immune response to an antigen, the method comprising administering to a subject an effective amount of a composition comprising a Listeria monocytogenes vaccine strain comprising said antigen fused to a PEST-like sequence selected from the group consisting of the sequences set forth in SEQ ID No: 2-5, wherein said antigen is selected from human papilloma virus (HPV) E6, HPV E7, Her-2/Neu, NY-ESO-1, human telomerase, WT-1, proteinase 3, TRP-2, and PSA antigen.
14. The method of claim 13 , wherein said subject is a human.
15. The method of claim 13 , wherein said composition is suspended in a pharmaceutically acceptable carrier.
16. The Listeria monocytogenes vaccine strain of claim 1 , wherein said truncated ActA comprises a PEST-like sequence as set forth in SEQ ID No: 2.
17. The method of claim 6 , wherein said truncated ActA comprises a PEST-like sequence as set forth in SEQ ID No: 2.
18. The Listeria monocytogenes vaccine strain of claim 9 , wherein said PEST-like sequence is set forth in SEQ ID No: 2.
19. The method of claim 13 , wherein said PEST-like sequence is set forth in SEQ ID No: 2.