Methods and compositions for stimulating immune response
The present invention relates to methods and compositions for stimulating an immune response. In particular, the present invention relates to immunostimulatory RNA molecules comprising sequences derived from an Influenza A virus nucleoprotein-encoding RNA molecule that act as adjuvants and/or immunostimulatory agents to enhance host immune responses.
1. A method for stimulating an immune response in a subject comprising providing to the subject at least one antigen and providing an immunostimulatory RNA molecule, the immunostimulatory RNA molecule comprising (i) a sequence selected from the group consisting of the sequence of SEQ ID NO: 1, the sequence of SEQ ID NO: 2, and the sequence of SEQ ID NO: 5, and, wherein said immunostimulatory RNA molecule optionally further comprises the sequence of SEQ ID NO: 3 or the sequence of SEQ ID NO: 4; or (ii) a sequence selected from the group consisting of the sequence of SEQ ID NO: 6, the sequence of SEQ ID NO: 7, the sequence of SEQ ID NO: 8, the sequence of SEQ ID NO: 9, the sequence of SEQ ID NO: 10, and the sequence of SEQ ID NO: 11.
2. The method of claim 1 , wherein the immunostimulatory RNA molecule is capable of inducing an antigen specific immune response in the subject.
3. The method of claim 1 , wherein the immune response comprises a B cell response.
4. The method of claim 1 , wherein the immune response comprises the production of IgG antibodies associated with a Th1-like response.
5. The method of claim 1 , wherein the immunostimulatory RNA molecule is a toll-like receptor (TLR) agonist.
6. The method of claim 5 , wherein the TLR is TLR7.
7. The method of claim 1 , wherein the immunostimulatory RNA molecule is capable of inducing secretion of interferon alpha.
8. The method of claim 7 , wherein secretion of interferon alpha involves plasmacytoid dendritic cells.
9. The method of claim 1 , wherein the immunostimulatory RNA molecule does not substantially induce secretion of one or more of tumor necrosis factor alpha, interferon gamma and interleukin 10.
10. The method of claim 1 , wherein the at least one antigen is selected from the group consisting of cancer, virus, bacterial, fungal, or parasite antigens.
11. The method of claim 1 , wherein the subject is a mammal.
12. The method of claim 1 , wherein the subject is a human.
13. A method for stimulating an immune response in a subject comprising providing to the subject at least one antigen and providing an immunostimulatory RNA molecule, wherein the immunostimulatory RNA molecule is selected from the group consisting of SEQ ID NOs: 1, 5, 6, 7, 8, 9, 10, and 11.
14. The method of claim 13 , wherein the immunostimulatory RNA molecule is SEQ ID NO: 11.
15. The method of claim 13 , wherein the immunostimulatory RNA molecule is formulated in a liposomal formulation.
16. The method of claim 15 , wherein the liposomal formulation comprises 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) and 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE).
17. The method of claim 13 , wherein the at least one antigen is a tumor antigen.
18. The method of claim 17 , wherein the tumor antigen is Claudin-18.2 or Claudin-6.
19. A method for stimulating an immune response in a subject comprising providing to the subject at least one antigen and providing an immunostimulatory RNA molecule, the immunostimulatory RNA molecule comprising the sequence of SEQ ID NO: 1.
20. The method of claim 19 , wherein the immunostimulatory RNA molecule is formulated in a liposomal formulation.
21. The method of claim 20 , wherein the liposomal formulation comprises 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) and 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE).
22. The method of claim 19 , wherein the immunostimulatory RNA molecule comprises the sequence of SEQ ID NO: 11.
23. The method of claim 22 , wherein the immunostimulatory RNA molecule is formulated in a liposomal formulation.
24. The method of claim 23 , wherein the liposomal formulation comprises 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) and 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE).
25. The method of claim 19 , wherein the immunostimulatory RNA molecule comprises the sequence of SEQ ID NO: 11 and wherein the at least one antigen is a tumor antigen.
26. The method of claim 25 , wherein the tumor antigen is Claudin-18.2 or Claudin-6.
27. The method of claim 25 , wherein the immunostimulatory RNA molecule is formulated in a liposomal formulation.
28. The method of claim 27 , wherein the liposomal formulation comprises 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) and 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE).
29. The method of claim 14 , wherein the immunostimulatory RNA molecule is formulated in a liposomal formulation.
30. The method of claim 29 , wherein the liposomal formulation comprises 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) and 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE).