Immunostimulatory nucleic acid molecules
View Patent ↗Nucleic acids containing unmethylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response and to redirect a Th2 response to a Th1 response in a subject are disclosed. Methods for treating atopic diseases, including atopic dermatitis, are disclosed.
1. An immunostimulatory nucleic acid composition comprising
an immunostimulatory nucleic acid represented by the formula 5′ X 1 X 2 CGX 3 X 4 3′ encapsulated within a lipid,
wherein C is unmethylated, and X 1 , X 2 , X 3 and X 4 are nucleotides, and wherein the immunostimulatory nucleic acid is 8-100 nucleotides in length.
2. The composition of claim 1 , wherein the lipid is a cationic lipid or a liposome.
3. The composition of claim 1 or 2 , wherein the immunostimulatory nucleic acid is 8-40 nucleotides in length.
4. The composition of claim 1 or 2 , wherein the immunostimulatory nucleic acid has a phosphodiester backbone.
5. The composition of claim 1 or 2 , further comprising an antigen.
6. The composition of claim 5 , wherein the immunostimulatory nucleic acid has a phosphodiester backbone.
7. A method for stimulating an immune response to a vaccine comprising
administering to a subject a composition comprising an immunostimulatory nucleic acid 8-100 nucleotides in length represented by the formula 5′ X 1 X 2 CGX 3 X 4 3′ encapsulated within a lipid, wherein C is unmethylated, and X 1 , X 2 , X 3 and X 4 are nucleotides, and an antigen, in an amount effective to boost the subject's immune response to the vaccine.
8. The method of claim 7 , wherein the lipid is a cationic lipid or a liposome.
9. The method of claim 7 or 8 , wherein the immunostimulatory nucleic acid is 8-40 nucleotides in length.
10. A composition comprising
an antigen and an immunostimulatory nucleic acid associated with a liposome, wherein the immunostimulatory nucleic acid is represented by the formula 5′ X 1 X 2 CGX 3 X 4 3′, wherein C is unmethylated, and X 1 , X 2 , X 3 and X 4 are nucleotides, wherein the antigen is selected from the group consisting of proteins, polysaccharides, polysaccharide conjugates, glycolipids, viruses, bacteria, fungi, parasites, and allergens, wherein the immunostimulatory nucleic acid is 8-100 nucleotides in length.
11. A composition comprising
an antigen and an immunostimulatory nucleic acid associated with a liposome, wherein the immunostimulatory nucleic acid is represented by the formula 5′ X 1 X 2 CGX 3 X 4 3′, wherein C is unmethylated, and X 1 , X 2 , X 3 and X 4 are nucleotides, wherein the antigen is derived from an infectious organism selected from the group consisting of infectious bacteria, infectious virus, or infectious fungi, wherein the immunostimulatory nucleic acid is 8-100 nucleotides in length.
12. A composition comprising
an antigen and an immunostimulatory nucleic acid encapsulated in a liposome, wherein the immunostimulatory nucleic acid is represented by the formula 5′ X 1 X 2 CGX 3 X 4 3′, wherein C is unmethylated, and X 1 , X 2 , X 3 and X 4 are nucleotides, wherein the antigen is selected from the group consisting of proteins, polysaccharides, polysaccharide conjugates, glycolipids, viruses, bacteria, fungi, parasites, and allergens, wherein the immunostimulatory nucleic acid is 8-100 nucleotides in length.
13. A composition comprising
an antigen and an immunostimulatory nucleic acid encapsulated in a liposome, wherein the immunostimulatory nucleic acid is represented by the formula 5′ X 1 X 2 CGX 3 X 4 3′, wherein C is unmethylated, and X 1 , X 2 , X 3 and X 4 are nucleotides, wherein the antigen is derived from an infectious organism selected from the group consisting of infectious bacteria, infectious virus, or infectious fungi, wherein the immunostimulatory nucleic acid is 8-100 nucleotides in length.
14. The composition of claim 10 , 11 , 12 or 13 , wherein 5′ X 1 X 2 CGX 3 X 4 3′ is not a palindrome.
15. The composition of claim 10 , 11 , 12 or 13 , wherein the immunostimulatory nucleic acid is not an antisense oligonucleotide.
16. The composition of claim 10 , 11 , 12 or 13 , wherein the immunostimulatory nucleic acid is 8-40 nucleotides in length.
17. The composition of claim 14 , wherein the immunostimulatory nucleic acid is 8-40 nucleotides in length.
18. The composition of claim 15 , wherein the immunostimulatory nucleic acid is 8-40 nucleotides in length.
19. A method of inducing an antigen-specific immune response in a subject comprising
administering to a subject the composition of claim 10 , 11 , 12 or 13 ,
in an amount effective to induce an antigen-specific immune response.
20. A method of inducing an antigen-specific immune response in a subject comprising administering to a subject the composition of claim 10 , 11 , 12 or 13 , wherein 5′ X 1 X 2 CGX 3 X 4 3′ is not a palindrome.
21. A method of inducing an antigen-specific immune response in a subject comprising administering to a subject the composition of claim 10 , 11 , 12 or 13 , wherein the immunostimulatory nucleic acid is not an antisense oligonucleotide.
22. The method of claim 19 , wherein the immunostimulatory nucleic acid is 8-40 nucleotides in length.
23. The method of claim 19 , wherein the composition is administered by oral, subcutaneous, intravenous, intraperitoneal or intrathecal route.
24. The method of claim 20 , wherein the immunostimulatory nucleic acid is 8-40 nucleotides in length.
25. The method of claim 21 , wherein the immunostimulatory nucleic acid is 8-40 nucleotides in length.
26. A method of inducing an antigen-specific immune response in a subject comprising
administering to a subject the composition of claim 5 in an amount effective to induce an antigen-specific immune response.