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. An isolated RNA molecule comprising:
(i) the sequence of SEQ ID NO: 6 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 6;
(ii) the sequence of SEQ ID NO: 7 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 7;
(iii) the sequence of SEQ ID NO: 10 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 10; or
(iv) the sequence of SEQ ID NO: 11 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 11;
wherein the isolated RNA molecule comprises a modification which is not naturally present in the RNA.
2. The isolated RNA molecule of claim 1 , wherein the isolated RNA molecule has immunostimulatory activity.
3. A pharmaceutical composition comprising the isolated RNA molecule of claim 1 and a pharmaceutically acceptable carrier.
4. The pharmaceutical composition of claim 3 , further comprising at least one antigen or a nucleic acid coding for at least one antigen.
5. The isolated RNA molecule of claim 1 , wherein the modification is:
a removed uncapped 5′-triphosphate,
partial or complete substitution of 5-methylcytidine for cytidine,
partial or complete substitution of pseudouridine for uridine, or
a 5′-cap or a 5′-cap analog.
6. The isolated RNA molecule of claim 1 , wherein the RNA is formulated in a nanoparticulate formulation.
7. The isolated RNA molecule of claim 6 , wherein the nanoparticulate formulation is a liposomal formulation or a lipoplex formulation.
8. A pharmaceutical composition comprising the isolated RNA molecule of claim 1 and at least one antigen or a nucleic acid coding for at least one antigen, wherein the antigen is not an influenza antigen.
9. The pharmaceutical composition of claim 8 , wherein the antigen is a cancer antigen, a bacterial antigen, a fungal antigen, a parasite antigen, an allergen or a self-antigen.
10. An isolated RNA molecule comprising:
(i) a variant of the sequence of SEQ ID NO: 6, said variant having at least 90% sequence identity to SEQ ID NO: 6;
(ii) a variant of the sequence of SEQ ID NO: 7, said variant having at least 90% sequence identity to SEQ ID NO: 7;
(iii) a variant of the sequence of SEQ ID NO: 10, said variant having at least 90% sequence identity to SEQ ID NO: 10; or
(iv) a variant of the sequence of SEQ ID NO: 11 of, said variant having at least 90% sequence identity to SEQ ID NO: 11.
11. A pharmaceutical composition comprising the isolated RNA molecule of claim 10 and a pharmaceutically acceptable carrier.
12. The pharmaceutical composition of claim 11 , further comprising at least one antigen or a nucleic acid coding for at least one antigen.
13. The isolated RNA molecule of claim 10 , wherein the RNA is formulated in a nanoparticulate formulation.
14. The isolated RNA molecule of claim 13 , wherein the nanoparticulate formulation is a liposomal formulation or a lipoplex formulation.
15. A pharmaceutical composition comprising the isolated RNA molecule of claim 10 and at least one antigen or a nucleic acid coding for at least one antigen, wherein the antigen is not an influenza antigen.
16. The pharmaceutical composition of claim 15 , wherein the antigen is a cancer antigen, a bacterial antigen, a fungal antigen, a parasite antigen, an allergen or a self-antigen.
17. An isolated RNA molecule comprising:
(i) the sequence of SEQ ID NO: 6 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 6;
(ii) the sequence of SEQ ID NO: 7 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 7;
(iii) the sequence of SEQ ID NO: 10 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 10; or
(iv) the sequence of SEQ ID NO: 11 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 11;
wherein the RNA is formulated in a nanoparticulate formulation.
18. The isolated RNA molecule of claim 17 , wherein the isolated RNA molecule has immunostimulatory activity.
19. A pharmaceutical composition comprising the isolated RNA molecule of claim 17 and a pharmaceutically acceptable carrier.
20. The pharmaceutical composition of claim 19 , further comprising at least one antigen or a nucleic acid coding for at least one antigen.
21. The isolated RNA molecule of claim 17 , wherein the nanoparticulate formulation is a liposomal formulation or a lipoplex formulation.
22. A pharmaceutical composition comprising the isolated RNA molecule of claim 17 and at least one antigen or a nucleic acid coding for at least one antigen, wherein the antigen is not an influenza antigen.
23. The pharmaceutical composition of claim 22 , wherein the antigen is a cancer antigen, a bacterial antigen, a fungal antigen, a parasite antigen, an allergen or a self-antigen.
24. A pharmaceutical composition comprising:
an isolated RNA molecule comprising:
(i) the sequence of SEQ ID NO: 6 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 6;
(ii) the sequence of SEQ ID NO: 7 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 7;
(iii) the sequence of SEQ ID NO: 10 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 10; or
(iv) the sequence of SEQ ID NO: 11 or a variant thereof, said variant having at least 90% sequence identity to SEQ ID NO: 11; and
at least one antigen or a nucleic acid coding for at least one antigen, wherein the antigen is not an influenza antigen.