Methods and compositions for nanoemulsion vaccine formulations
The present disclosure relates to nanoemulsion vaccine compositions and methods of making and using the same. The disclosed compositions and methods provide a means of treating, preventing, or protecting an individual from anthrax exposure or poisoning.
1. An aqueous composition consisting of:
(1) a recombinant protective antigen (rPA) of anthrax, wherein the rPA is present in a concentration of from about 50 μg/mL to about 750 μg/mL,
(2) a nanoemulsion, and
(3) a stabilizing system, wherein the stabilizing system consists of:
(a) tris(hydroxymethyl)aminomethane (TRIS) buffer;
(b) at least one salt;
(c) glycerol or at least one sugar selected from the group consisting of trehalose and sucrose;
(d) histidine; and
(e) optionally, at least one antioxidant;
wherein the composition preserves the potency of the rPA antigen by protecting it from degradation over time as compared to a composition comprising rPA and a nanoemulsion but lacking the stabilizing system, and
wherein the preserved potency is demonstrated by the formulation retaining at least about 80% rPA following storage at about 5° C. for at least 12 months as determined by RP-HPLC and/or SEC-HPLC.
2. The composition of claim 1 , wherein the composition consists of rPA, the nanoemulsion, and the stabilizing system.
3. The composition of claim 1 , wherein the rPA is in a concentration of from about 100 μg/ml to about 500 μg/ml.
4. The composition of claim 1 , wherein the nanoemulsion is W 80 5EC nanoemulsion adjuvant.
5. The composition of claim 4 , wherein the W 80 5EC nanoemulsion adjuvant is in a concentration of about 20%.
6. The composition of claim 1 , wherein the TRIS buffer is in a concentration of about 5 to about 100 mM.
7. The composition of claim 6 , wherein the TRIS buffer is in a concentration of about 10 mM.
8. The composition of claim 6 , wherein the TRIS buffer is in a concentration of about 80 mM.
9. The composition of claim 1 , wherein the salt is sodium chloride.
10. The composition of claim 9 , wherein the sodium chloride is in a concentration of about 50 to about 150 mM.
11. The composition of claim 1 , wherein the salt is calcium chloride.
12. The composition of claim 11 , wherein the calcium chloride is in a concentration of about 50 to about 150 mM.
13. The composition of claim 1 , wherein the sugar is trehalose.
14. The composition of claim 13 , wherein the trehalose is in a concentration of about 5 to about 15%.
15. The composition of claim 1 , wherein the histidine is in a concentration of about 20 to about 70 mM.
16. The composition of claim 15 , wherein the histidine is in a concentration of about 60 mM.
17. A method of eliciting an immune response in a subject, comprising administering to a subject in need thereof an effective amount of the composition of claim 1 .
18. The method of claim 17 , wherein the subject is at risk of being exposed to anthrax.
19. The method of claim 17 , wherein the composition is administered intranasally.
20. The composition of claim 1 , wherein the sugar is sucrose.
21. The composition of claim 20 , wherein the sucrose is in a concentration of about 5 to about 15%.
22. The composition of claim 1 , wherein the sugar is sucrose at a concentration of about 5% to about 15%, and the amino acid is histidine at a concentration of about 20 mM to about 70 mM.
23. The composition of claim 1 , wherein TRIS is at a concentration of about 10 mM, the sugar is sucrose at a concentration of about 5% to about 15%, and the amino acid is histidine at a concentration of about 20 mM to about 70 mM.
24. The composition of claim 1 , wherein the rPA does not comprise a chemically modified thiol group.
25. The composition of claim 1 , wherein the preserved potency is demonstrated by the formulation retaining at least about 80% rPA following storage at about 25° C. for at least 6 months as determined by RP-HPLC and/or SEC-HPLC.
26. The composition of claim 1 , wherein the preserved potency is demonstrated by the formulation retaining at least about 80% rPA following storage at about −20° C. for at least 6 months as determined by RP-HPLC and/or SEC-HPLC.
27. The composition of claim 1 , wherein the preserved potency is demonstrated by the formulation retaining at least about 80% rPA following storage at about −20° C. for at least 12 months as determined by RP-HPLC and/or SEC-HPLC.