Vaccine 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 pharmaceutical composition comprising a glucopyranosyl lipid adjuvant (GLA) having the formula:
where: R1, R3, R5 and R6 are C11-C20 alkyl; and R2 and R4 are C12-C20 alkyl; or a pharmaceutically acceptable salt thereof; at least one of a surfactant and a biodegradable oil; and a pharmaceutically acceptable carrier, excipient or diluent.
2. The composition of claim 1 in an emulsion form.
3. The composition of claim 1 in an oil-in-water emulsion form.
4. The composition of claim 3 comprising squalene.
5. The composition of any one of claims 1 - 4 further comprising at least one additional component selected from the group consisting of:
a toll-like receptor (TLR) agonist;
a saponin or saponin mimetic;
a co-adjuvant; and
a carrier that comprises at least one of an oil and an immunostimulatory complex.
6. The composition of claim 5 wherein the saponin comprises QS21.
7. The composition of any one of claims 1 - 4 comprising oil droplets having a size of less than 1 micron in diameter.
8. The composition of claim 1 in a liquid form.
9. The composition of claim 1 or 8 in a solution form or in a suspension form.
10. The composition of claim 1 or 8 comprising a stable aqueous suspension of particles of less than 0.2 μm diameter and at least one component selected from the group consisting of phospholipid, fatty acid, surfactant, detergent, saponin, and fluoridated lipid.
11. The composition of claim 1 or 8 comprising liposomes.
12. The composition of claim 1 or 8 comprising microspheres.
13. The composition of claim 1 in an aerosol form.
14. The composition of claim 1 in a lyophilizate form.
15. The composition of any one of claims 1 - 4 , 6 , 8 , 13 and 14 comprising a preservative, an antibacterial agent, or an antioxidant, or any combination of the foregoing.
16. The composition of claim 1 comprising a dispersing agent and/or a suspending agent.
17. The composition of claim 1 comprising a buffer.
18. The composition of claim 1 comprising sterile water.
19. The composition of claim 1 comprising alpha tocopherol.
20. The composition of claim 1 comprising a synthetic mono or diglyceride.
21. The composition of claim 1 comprising an aluminum salt.
22. The composition of claim 1 comprising a recombinant viral vector.
23. The composition of claim 1 comprising at least one of petrolatum, lanolin, polyethylene glycol, beeswax, and mineral oil.
24. The composition of claim 1 formulated for injection.
25. The composition of any one of claims 1 - 4 , 6 , 8 , 13 and 14 , and 16 - 24 wherein: R1, R3, R5 and R6 are undecyl; and R2 and R4 are tridecyl.
26. The composition of claim 1 wherein the GLA is a pharmaceutically acceptable salt.
27. The composition of claim 25 wherein the GLA is a pharmaceutically acceptable salt.