Immunostimulatory oligonucleotides
The invention relates to immunostimulatory oligonucleotides and methods of using immunostimulatory oligonucleotides to induce an antigen-specific immune response. The invention further relates to a vaccine that comprises an immunostimulatory oligonucleotide and an antigen, and comprises a pharmaceutically acceptable carrier. The immunostimulatory oligonucleotides of the invention, in some embodiments, include one or more modified linkage(s).
1. A composition comprising an antigen and an immunostimulatory oligonucleotide comprising the nucleotide sequence of SEQ ID NO: 1, and further comprising a pharmaceutically acceptable carrier.
2. The composition of claim 1 , wherein the immunostimulatory oligonucleotide is in an effective amount to induce an antigen-specific immune response.
3. The composition of claim 2 , wherein the antigen-specific immune response induced is a Th1 immune response.
4. The composition of claim 1 , wherein the antigen is a microbial antigen, a self antigen or an addictive substance.
5. The composition of claim 4 , wherein the microbial antigen is a bacterial antigen, a viral antigen or a parasitic antigen.
6. The composition of claim 5 , wherein the bacterial antigen is associated with Staphylococcus aureus.
7. The composition of claim 5 , wherein the viral antigen is associated with Respiratory Syncytial virus (RSV), Herpes Simplex virus 1, Herpes Simplex virus 2, Human Immunodeficiency Virus-1 (HIV-1) or HIV-2.
8. The composition of claim 4 , wherein the self antigen is a tumor antigen, an antigen associated with Alzheimer's Disease, an antigen against a human antibody, or an antigen that is expressed from human endogenous retroviral elements.
9. The composition of claim 8 , wherein the tumor antigen is HER2, MAGE, NY-ESO, PSA, CEA or a variant form of EGFR.
10. The composition of claim 8 , wherein the antigen is IgE.
11. The composition of claim 4 , wherein the antigen is a nicotine hapten conjugated to a carrier.
12. The composition of claim 11 , wherein the carrier to which the nicotine hapten is conjugated is diphtheria toxin (DT).
13. The composition of claim 1 , wherein the antigen is a peptide, a recombinant protein, a purified protein, whole killed pathogen, live attenuated virus or viral vector, live attenuated bacteria or a bacterial vector, a polysaccharide, a hapten, or encoded by plasmid DNA.
14. The composition of claim 1 , wherein the antigen is conjugated to a carrier.
15. The composition of claim 14 , wherein the carrier is diphtheria toxin (DT) or a virus-like particle.
16. The composition of claim 15 , wherein the virus-like particle is RNA phage Q-β, hepatitis B surface antigen (HBsAg), or hepatitis B core antigen (HbcAg).
17. The composition of claim 1 , further comprising one or more adjuvants.
18. The composition of claim 17 , wherein the adjuvant is an aluminum salt.
19. The composition of claim 18 , wherein the aluminum salt is aluminum hydroxide.
20. The composition of claim 17 , wherein the adjuvant is a liposome.
21. The composition of claim 1 , wherein the immunostimulatory oligonucleotide comprises one or more phosphorothioate linkages.
22. The composition of claim 1 , wherein the immunostimulatory oligonucleotide comprises at least one lipophilic substituted nucleotide analog and a pyrimidine-purine dinucleotide.
23. The composition of claim 1 , wherein the composition is formulated for administration via a parenteral route, wherein the parenteral route is intramuscular, subcutaneous, intradermal, intravenous or intraperitoneal.
24. The composition of claim 1 , wherein the composition is formulated for administration via a topical route, wherein the topical route is the skin, transdermal or a mucosal surface.