Vaccines and immunotherapeutics using codon-optimized IL-15 and methods for using the same
View Patent ↗Nucleic acid molecules that encode IL-15 or fragments thereof, which express protein at a higher level than nucleic acid molecules with native coding sequences for IL-15 are disclosed. Nucleic acid molecules with additional modifications such as the absence of coding sequences for IL-15 signal sequences and/or the absence of IL-15 untranslated sequences and/or inclusion of non-IL-15 signal sequences are also disclosed. Vectors, including plasmids and viral vectors, comprising such nucleic acid molecules; and to host cells comprising such nucleic acid molecules are disclosed as well as methods of using such nucleic acid molecules alone or in combination with nucleic acid sequences encoding immunogens which are part of the nucleic acid molecules and/or part of a different nucleic acid molecule. Recombinant vaccines and live attenuated pathogens encoding fusion proteins, and methods of using the same, are disclosed.
1. An isolated nucleic acid molecule comprising nucleotides 67-420 of SEQ ID NO: 1.
2. The nucleic acid molecule of claim 1 free of coding sequence for an IL-15 signal sequence.
3. The nucleic acid molecule of claim 1 of IL-15 Kozak region and/or IL-15 5′ untranslated region and/or IL-15 3′ untranslated region.
4. The nucleic acid molecule of claim 1 comprising a coding sequence for a non-IL-15 signal sequence.
5. The nucleic acid molecule of claim 1 comprising a coding sequence for an IgE signal sequence.
6. The nucleic acid molecule of claim 1 further comprising coding sequence for an immunogen.
7. The nucleic acid molecule of claim 6 wherein said immunogen is a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases.
8. The isolated nucleic acid molecule of claim 7 wherein said immunogen is a pathogen antigen from a pathogen selected from the group consisting of HIV, HSV, HCV, and WNV.
9. The isolated nucleic acid molecule of claim 1 wherein said isolated nucleic acid molecule is a plasmid.
10. The nucleic acid molecule of claim 1 incorporated into a viral vector.
11. The nucleic acid molecule of claim 1 incorporated into a live attenuated pathogen.
12. A composition comprising a nucleic acid molecule of claim 1 and a nucleic acid molecule that comprises a nucleic acid sequence that encodes an immunogen.
13. The composition of claim 12 wherein said immunogen is a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases.
14. The composition of claim 13 wherein said immunogen is a pathogen antigen from a pathogen selected from the group consisting of HIV, HSV, HCV, and WNV.
15. The composition of claim 12 wherein said nucleic acid molecules are plasmids.
16. An injectable pharmaceutical composition comprising the nucleic acid molecules of claim 1 .
17. A method of modulating an immune response in an individual comprising administering to said individual a nucleic acid molecule of claim 1 .
18. A recombinant vaccine comprising a nucleic acid sequence that encodes an immunogen and a nucleic acid sequence of claim 1 .
19. The recombinant vaccine of claim 18 wherein said immunogen is a pathogen antigen, a cancer-associated antigen or an antigen linked to cells associated with autoimmune diseases.
20. The recombinant vaccine of claim 19 wherein said immunogen is a pathogen antigen from a pathogen selected from the group consisting of HIV, HSV, HCV, and WNV.
21. The recombinant vaccine of claim 18 wherein said recombinant vaccine is a recombinant vaccinia vaccine.
22. A method of inducing an immune response in an individual against an immunogen comprising administering to said individual a nucleic acid molecule of claim 6 .
23. A method of inducing an immune response in an individual against an immunogen comprising administering to said individual a composition of claim 12 .
24. A method of inducing an immune response in an individual against an immunogen comprising administering to said individual a recombinant vaccine of claim 18 .
25. An injectable pharmaceutical composition comprising the composition of claim 12 .