Immunostimulatory oligonucleotides
Compositions that include immunostimulatory nucleic acids are disclosed, along with the use of such compositions to induce immune responses.
1. A composition comprising:
an immunostimulatory isolated nucleic acid comprising a sequence:
[SEQ ID NO. 1]
5′-TCGTCGAACGTTCGCGAACGTTCG-3′;
and
a pharmaceutically acceptable excipient;
wherein C is unmethylated.
2. The composition of claim 1 , wherein the immunostimulatory isolated nucleic acid further comprises a stabilizing modification.
3. The composition of claim 2 , wherein the stabilizing modification comprises modifications of 3′ OH or 5′ OH groups, modifications of nucleotide bases, modifications of sugar components, or modifications of phosphate groups.
4. The composition of claim 2 , wherein the stabilizing modification comprises a phosphorothioate backbone.
5. The composition of claim 1 , further comprising an antigen.
6. The composition of claim 5 , wherein the antigen comprises a B cell antigen.
7. The composition of claim 5 , wherein the antigen comprises a T cell antigen.
8. The composition of claim 7 , wherein the T cell antigen comprises a T helper cell antigen.
9. The composition of claim 6 , wherein the B cell antigen comprises one or more of a protein, peptide, small molecule, and a carbohydrate.
10. The composition of claim 1 , further comprising a carrier coupled to the immunostimulatory isolated nucleic acid.
11. The composition of claim 10 , wherein the carrier comprises a protein carrier.
12. The composition of claim 10 , wherein the carrier comprises a synthetic nanocarrier.
13. The composition of claim 12 , wherein the synthetic nanocarrier is additionally coupled to an antigen.
14. The composition of claim 12 , further comprising an additional synthetic nanocarrier not coupled to the immunostimulatory isolated nucleic acid.
15. The composition of claim 14 , wherein the additional synthetic nanocarrier is coupled to an antigen.
16. The composition of claim 15 , wherein the antigen comprises a T helper cell antigen.
17. The composition of claim 1 , wherein the immunostimulatory isolated nucleic acid consists essentially of:
[SEQ ID NO. 1]
5′-TCGTCGAACGTTCGCGAACGTTCG-3′.
18. The composition of claim 1 , wherein the immunostimulatory isolated nucleic acid does not comprise a stabilizing modification.
19. The composition of claim 1 , wherein the immunostimulatory nucleic acid consists of SEQ ID NO:1.
20. A method of inducing IL-6 production in a subject, the method comprising administering to the subject the composition of claim 1 in an amount effective amount to induce IL-6 in the subject.
21. A method for inducing interferon-alpha in a subject, the method comprising administering to the subject the composition of claim 1 in an amount effective to induce interferon-alpha production in the subject.
22. A method for inducing IP-10 in a subject, the method comprising administering to the subject the composition of claim 1 in an amount effective to induce IP-10 production in the subject.
23. A method comprising:
administering the composition of claim 1 to a subject.
24. A composition comprising
a vaccine that comprises the composition of claim 1 .
25. An isolated nucleic acid comprising SEQ ID NO:1.
26. An isolated nucleic acid consisting of SEQ ID NO:1.
27. A method comprising:
administering to a subject an amount of the composition of claim 6 effective to induce an antibody response against the antigen.