Long term disease modification using immunostimulatory oligonucleotides
The invention provides methods for treating asthma by using multiple rounds of administration of ISS over a period of time to confer long term disease modification.
1. A method for treating an individual in need thereof comprising administering to the individual multiple administrations of an effective amount of an ISS wherein the ISS is administered at least 5 times and wherein the administration results in a long term disease modification of allergic rhinitis, wherein the long term disease modification is determined by the reduction of one or more allergic rhinitis symptoms for a period of at least 3 weeks after the last administration of the ISS, wherein the ISS is administered to the individual from about 3 days to about 4 weeks in between the dosages, and wherein the ISS comprises 5′-N x (TCG(N q )) y N w (X 1 X 2 CGX 2 ′X 1 ′(CG) p ) z (SEQ ID NO:14) wherein N are nucleosides with x =0-3, y =1-4, w =−2, −1, 0, 1 or 2, p=0 or 1, q =0, 1 or 2, and z =1-20, wherein X 1 and X 1 ′,X 2 and X 2 ′ are self-complimentary, and wherein the 5′ T of the (TCG(N g )) y (SEQ ID NO:3) sequence is 0-3 bases from the 5′ end of the polynucleotide.
2. The method of claim 1 wherein the multiple administrations occur on a weekly basis.
3. The method of claim 1 wherein the ISS is administered every 14 days.
4. The method of claim 1 wherein the long term disease modification is a decrease of Th2 response in the individual.
5. The method of claim 4 wherein the decrease of Th2 response in the individual is a decrease of any one of the cytokines selected from group consisting of IL-4, IL-5, IL-10, and IL-13.
6. The method of claim 1 wherein the long term disease modification lasts at least 13 weeks after the last administration of the ISS.
7. The method of claim 1 wherein the individual in need thereof has allergic rhinitis.
8. The method of claim 1 wherein the ISS is administered in the presence of an allergen.
9. The method of claim 8 wherein the allergen is an adventitious allergen.
10. The method of claim 9 wherein the adventitious allergen is ragweed.
11. The method of claim 8 wherein the allergen is a seasonal allergen.
12. The method of claim 1 wherein the individual is a human with allergic rhinitis but not asthma.
13. The method of claim 4 wherein the decrease of Th2 response in an individual is a decrease in eosinophil infiltration in the airways.
14. The method of claim 1 wherein the modification lasts at least 8 weeks after the last administration of the ISS.
15. The method of claim 1 wherein the ISS is an unconjugated ISS.
16. The method of claim 1 wherein the ISS comprises phosphorothioate linkages.
17. The method of claim 1 wherein the CpG-containing ISS is administered at least 8 times.
18. The method of claim 1 wherein the ISS is less than 200 bases in length.