Compositions of vaccines and adjuvants and methods for the treatment of urinary tract infections
This invention describes novel adjuvant compositions and formulations with excellent stability at refrigerated and room temperatures and up to and about 37° C. that can be produced at remarkably low costs. This invention describes novel vaccine compositions and formulations to treat and prevent urinary tract infections caused by gram-negative bacteria including Escherichia coli and multi-drug resistant E. coli . This invention also describes methods of administration of said novel vaccine compositions and formulations and methods of treatment to prevent and treat urinary tract infections caused by gram-negative bacteria including E. coli and multi-drug resistant E. coli.
1. A method for administering a vaccine composition to a human comprising the steps of:
administering to the human a vaccine composition comprising an adjuvant formulation comprising about 20 μg to about 50 μg of phosphorylated hexaacyl disaccharide, a phosphatidylcholine, and a buffer selected from the group consisting of citrate and succinate from about 10 mM to about 50 mM, wherein the phosphatidylcholine is at a molar ratio with phosphorylated hexaacyl disaccharide at about 1:1 to about 20:1, and the vaccine composition is an aqueous buffered suspension.
2. The method of claim 1 , wherein the phosphorylated hexaacyl disaccharide is present in an amount from about 40 μg to about 50 μg.
3. The method of claim 1 , wherein the buffer is at a concentration of 15 mM to about 50 mM.
4. The method of claim 1 , wherein the buffer is at a concentration of 20 mM to about 50 mM.
5. The method of claim 1 , wherein phosphorylated hexaacyl disaccharide is comprised of
6. The method of claim 1 , wherein the buffer is citrate.
7. The method of claim 1 , wherein the buffer is succinate.
8. The method of claim 1 , wherein the vaccine composition comprises an effective amount of FimCH or truncated FimH.
9. The method of claim 1 , wherein the vaccine composition comprises an effective amount of FimCH.
10. The method of claim 1 , wherein the vaccine composition is for the treatment of recurrent urinary tract infections.
11. The method of claim 1 , wherein phosphatidylcholine is selected from the group consisting of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC).
12. The method of claim 1 , wherein the phosphatidylcholine is selected from the group consisting of DMPC, DPPC, and DSPC.
13. The method of claim 1 , wherein the phosphatidylcholine is at a molar ratio with phosphorylated hexaacyl disaccharide at about 2:1 to about 5:1.
14. The method of claim 11 , wherein the phosphatidylcholine is at a molar ratio with phosphorylated hexaacyl disaccharide at about 2:1 to about 5:1.
15. The method of claim 12 , wherein the phosphatidylcholine is at a molar ratio with phosphorylated hexaacyl disaccharide at about 2:1 to about 5:1.
16. The method of claim 1 , wherein the vaccine composition has a mean particle size of 150 nanometers or less.
17. The method of claim 1 , wherein the vaccine composition is essentially free of a second adjuvant.
18. The method of claim 1 , wherein the vaccine composition is substantially free of saline.
19. The method of claim 18 , wherein the phosphorylated hexaacyl disaccharide is comprised of
20. The method of claim 1 , wherein the vaccine composition is substantially free of cholesterol.
21. The method of claim 1 , wherein the vaccine composition is essentially free of cholesterol.
22. A method for administering a vaccine composition to a human comprising the steps of:
administering to the human a vaccine composition comprising an adjuvant formulation comprising about 20 μg to about 50 μg of phosphorylated hexaacyl disaccharide; phosphatidylcholine at a molar ratio with phosphorylated hexaacyl disaccharide at about 2:1 to about 5:1; phosphatidylcholine is selected from the group consisting of DMPC, DPPC, DSPC, POPC, and DOPC; and a buffer selected from the group consisting of citrate and succinate from 15 mM to about 50 mM, wherein the vaccine composition is an aqueous buffered suspension.
23. The method of claim 22 , wherein the phosphorylated hexaacyl disaccharide is comprised of
24. The method of claim 22 , wherein the buffer concentration is from 25 mM to about 50 mM.
25. The method of claim 22 , wherein the vaccine composition is essentially free of a second adjuvant.
26. The method of claim 22 , wherein the vaccine composition comprises an effective amount of FimCH or truncated FimH.
27. The method of claim 22 , wherein the vaccine composition comprises an effective amount of FimCH.
28. The method of claim 22 , wherein the vaccine composition comprises about 40 μg to about 50 μg of phosphorylated hexaacyl disaccharide, the buffer is citrate, and an effective amount of FimCH, wherein the vaccine composition is essentially free of a second adjuvant.
29. An adjuvant formulation for a vaccine comprising:
phosphorylated hexaacyl disaccharide;
a phosphatidylcholine; and,
a buffer selected from the group consisting of citrate and succinate,
wherein the buffer concentration is from about 10 mM to about 50 mM, and the phosphatidylcholine is at a molar ratio with phosphorylated hexaacyl disaccharide at about 1:1 to about 20:1.
30. The adjuvant formulation of claim 29 wherein the phosphorylated hexaacyl disaccharide is comprised of