Treatment of allergic conditions using a composition containing synthetic adjuvant
Compositions and methods, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response are disclosed based on the discovery of useful immunological adjuvant properties in a synthetic, glucopyranosyl lipid adjuvant (GLA) that is provided in substantially homogeneous form. Chemically defined, synthetic GLA offers a consistent vaccine component from lot to lot without the fluctuations in contaminants or activity that compromise natural-product adjuvants. Also provided are vaccines and pharmaceutical compositions that include GLA and one or more of an antigen, a Toll-like receptor (TLR) agonist, a co-adjuvant and a carrier such as a pharmaceutical carrier.
1. A method of treating an allergic condition in a subject comprising administering to the subject a composition comprising:
a glucopyranosyl lipid adjuvant (GLA), of the formula
where:
R 1 , R 3 , R 5 and R 6 are undecyl; and
R 2 and R 4 are tridecyl;
wherein said composition is substantially devoid of an antigen; and
wherein said composition stimulates an immune response in the subject thereby treating the allergic condition in the subject.
2. The method according to claim 1 wherein the pharmaceutically acceptable carrier is in the form of an oil-in-water emulsion.
3. The method according to claim 1 wherein the pharmaceutically acceptable carrier is in the form of a liposome.
4. The method according to claim 1 wherein the pharmaceutically acceptable carrier is in the form of a microparticle.
5. The method according to claim 1 wherein the pharmaceutically acceptable carrier is in the form of a water-in-oil emulsion.
6. The method according to claim 1 wherein the composition further comprises at least one additional toll-like receptor (TLR) agonist.
7. The method according to claim 6 wherein the TLR agonist is selected from the group consisting of lipopolysaccharide, peptidoglycan, polyI:C, CpG, 3M003 and flagellin.
8. The method according to claim 1 wherein the composition further comprises a saponin or saponin mimetic.
9. The method according to claim 1 wherein the composition further comprises squalene, squalane, mineral oil, olive oil, cholesterol or a mannide monooleate.
10. The method according to claim 1 wherein the composition further comprises an imidazoquinoline immune response modifier.
11. The method according to claim 10 wherein the imidazoquinoline immune response modifier is selected from the group consisting of resiquimod (R848), imiquimod and gardiquimod.
12. The method according to claim 1 wherein the composition further comprises a double stem loop immune modifier (dSLIM).
13. The method according to claim 1 wherein the composition further comprises an adjuvant.
14. The method according to claim 1 wherein
the composition further comprises alum, a plant alkaloid, a detergent, a cytokine, a detergent, a block copolymer or a biodegradable polymer.
15. The method according to claim 1 wherein the composition down regulates a Th2 immune response.
16. The method of claim 1 wherein the allergic condition is seasonal rhinitis.
17. A method of treating an allergic condition comprising administering to the individual an effective amount of a composition comprising GLA of the formula
where:
R 1 , R 3 , R 5 and R 6 are undecyl; and
R 2 and R 4 are tridecyl.
18. The method of claim 17 wherein the composition further comprises a second adjuvant that is a TLR agonist.
19. The method of claim 17 or 18 wherein the composition further comprises an antigen associated with allergy or asthma.
20. The method of claim 19 wherein the allergen comprises an antigen from a food product, pollen, tree pollen, grass pollen, a mite, a cat, or a stinging insect.