Compositions including β-glucans and methods of use
The invention generally relates to soluble beta-glucan compositions and method of using such compositions. In one aspect, an adjuvant for a pharmaceutical composition is described which includes a soluble beta-glucan and a TLR agonist, each in an amount that, in combination with the other, is effective to increase a subject's immune response to an antigen. In another aspect, compositions that generally include an antigen component, a soluble beta-glucan component, and a TLR agonist component and a method that generally includes administering to a subject a composition that comprises a soluble beta-glucan and a TLR agonist, each in an amount that, in combination with the other, is effective to increase a subject's immune response to an antigen, are described.
1. An adjuvant comprising:
a yeast-derived soluble β-glucan; and
an agonist of TLR 7, TLR 8, or TLR 9;
each in an amount that, in combination with the other, is effective to increase a subject's immune response to an antigen other than the TLR agonist.
2. The adjuvant of claim 1 wherein the TLR agonist comprises an agonist of one or more of TLR 7 and TLR 8.
3. The adjuvant of claim 1 wherein the TLR agonist comprises an agonist of TLR 9.
4. The adjuvant of claim 1 wherein at least one β-glucan is covalently bound to at least one TLR agonist.
5. The adjuvant of claim 1 wherein the soluble β-glucan comprises β(1,6)-[poly-1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose.
6. The adjuvant of claim 1 wherein the TLR agonist comprises one or more of CL097 and CPG2006.
7. A composition comprising:
an antigen component;
a yeast-derived soluble β-glucan component; and
a TLR agonist component comprising an agonist of TLR 7, TLR 8, or TLR 9.
8. The composition of claim 7 wherein the antigen component comprises a tumor antigen.
9. The composition of claim 7 wherein the antigen component comprises an antigen from an infectious pathogen.
10. The composition of claim 9 wherein the infectious pathogen comprises a bacterium, a virus, a parasite, or a fungus.
11. The composition of claim 7 wherein the antigen component comprises a vaccine.
12. The composition of claim 7 wherein the TLR agonist component comprises an agonist of one or more of TLR 7 and TLR 8.
13. The composition of claim 7 wherein the TLR agonist component comprises an agonist of TLR 9.
14. The composition of claim 7 wherein at least one yeast-derived soluble β-glucan component is covalently bound to at least one TLR agonist component.
15. The composition of claim 7 comprising at least two formulations, wherein one formulation comprises at least one component and a second formulation comprises at least one component absent from the first formulation.
16. The composition of claim 7 wherein the soluble β-glucan comprises β(1,6)-[poly-1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose.
17. A method comprising:
administering to a subject a composition that comprises:
a yeast-derived soluble β-glucan; and
an agonist of TLR 7, TLR 8, or TLR 9;
each in an amount that, in combination with the other, is effective to increase a subject's immune response to an antigen.
18. The method of claim 17 wherein the yeast-derived soluble β-glucan and the TLR agonist are administered in a single formulation.
19. The method of claim 18 wherein at least one yeast-derived soluble β-glucan is covalently bound to at least one TLR agonist.
20. The method of claim 17 wherein the yeast-derived soluble β-glucan and the TLR agonist are administered in separate formulations.
21. The method of claim 17 wherein the composition induces a TLR-induced immune response greater than the TLR-induced immune response induced by administering the TLR agonist without the yeast-derived soluble β-glucan.
22. The method of claim 17 wherein the composition induces a predetermined level of a TLR agonist-dependent immune response using less TLR agonist than is necessary to induce the predetermined level if the TLR agonist is administered without the yeast-derived soluble β-glucan.
23. The method of claim 17 wherein TLR-dependent side effects are reduced for a predetermined level of TLR-dependent immune response compared to the TLR-dependent side effects observed if the TLR agonist is administered without the yeast-derivedsoluble β-glucan.
24. The method of claim 21 wherein the TLR-induced immune response comprises B-cell proliferation.
25. The method of claim 21 wherein the TLR-induced immune response comprises proliferation of antigen-specific T-cells.
26. The method of claim 21 wherein the TLR-induced immune response comprises co-stimulatory marker expression.
27. The method of claim 17 wherein the antigen comprises a vaccine antigen.
28. The method of claim 17 wherein the antigen comprises a tumor antigen.
29. The method of claim 17 wherein the antigen comprises an antigen from an infectious pathogen.
30. The method of claim 29 wherein the infectious pathogen comprises a bacterium, a virus, a parasite, or a fungus.
31. The method of claim 17 wherein the soluble β-glucan comprises β(1,6)-[poly-1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose.