Heat stable vaccines
The invention is directed to an oral vaccine composed of a micronized freeze-dried rotavirus particle suspension with buffering excipients in a non-aqueous liquid. This IVT-06 formulation has imparted heat stability by protecting the virus at temperatures of 30° C. and 40° C. for at least twelve months. Extrapolations from the 12-month stability data indicate a shelf life of more than two years at 30° C., and six months at 50° C. In addition, for ease of administration, the formulated dose has a volume of 0.5 mL.
1. An immunogenic composition comprising:
an attenuated strain of a rotavirus at a titer of about 10 5.9 FFU/mL or higher;
arginine and sucrose at a ratio of from about 1:1.1-2.5;
less than or equal to about 1.2% moisture;
an approximate uniform particle size of about 5 μm or less;
a buffering agent; and
medium-chain triglyceride (MCT).
2. The composition of claim 1 , wherein the rotavirus includes one or more serotypes of rotavirus.
3. The composition of claim 1 , which comprises approximately 2-4% arginine (w/v).
4. The composition of claim 1 , which comprises approximately 4-6% arginine (w/v).
5. The composition of claim 1 , which comprises approximately 6-8% sucrose (w/v).
6. The composition of claim 1 , which comprises approximately 8-10% sucrose (w/v).
7. The composition of claim 1 , wherein the ratio of from about 1:1.1-2.0.
8. The composition of claim 1 , wherein the ratio of from about 1:1.1-1.75.
9. The composition of claim 1 , wherein the buffering agent comprises a mix of citrate and calcium carbonate, Tris, Hepes, phosphates, histidine, or a combination thereof.
10. The composition of claim 1 , wherein the buffering agent maintains the composition at a pH of about 7.0-8.0.
11. The composition of claim 1 , which is lyophilized.
12. The composition of claim 1 , which as a glass transition temperature of about 70° C. or higher.
13. The composition of claim 1 , which as a glass transition temperature of about 75° C. or higher.
14. The composition of claim 1 , which as a glass transition temperature of about 80° C. or higher.
15. The composition of claim 1 , which, when stored at about room temperature or higher for at least about twelve months, has no significant loss of efficacy.
16. The composition of claim 1 , which, when stored at about 30° C. or higher for at least about two years, has no significant loss of efficacy.
17. The composition of claim 1 , which, when stored at about 50° C. or higher for at least about six months, has no significant loss of efficacy.
18. The composition of claim 1 , which, when stored at about 50° C. or higher for at least about twelve months, has no significant loss of efficacy.
19. An immunogenic composition comprising:
an attenuated strain of a rotavirus at a titer of about 10 5.9 FFU/mL or higher;
less than or equal to about 1.2% moisture;
an approximate uniform particle size of about 5 μm or less;
a buffering agent; and
medium-chain triglyceride (MCT), wherein
the composition has a glass transition temperature of about 60° C. or higher.
20. The composition of claim 19 , wherein the rotavirus includes one or more serotypes of rotavirus.
21. The composition of claim 19 , which comprises approximately 2-4% arginine (w/v).
22. The composition of claim 19 , which comprises approximately 4-6% arginine (w/v).
23. The composition of claim 19 , which comprises approximately 6-8% sucrose (w/v).
24. The composition of claim 19 , which comprises approximately 8-10% sucrose (w/v).
25. The composition of claim 19 , arginine and sucrose at a ratio of from about 1:1.1-2.5.
26. The composition of claim 25 , wherein the ratio of from about 1:1.1-1.75.
27. The composition of claim 19 , wherein the buffering agent comprises a mix of citrate and calcium carbonate, Tris, Hepes, phosphates, histidine, or a combination thereof.
28. The composition of claim 19 , wherein the buffering agent maintains the composition at a pH of about 7.0-8.0.
29. The composition of claim 19 , which is lyophilized.
30. The composition of claim 19 , which as a glass transition temperature of about 70° C. or higher.
31. The composition of claim 19 , which as a glass transition temperature of about 75° C. or higher.
32. The composition of claim 19 , which as a glass transition temperature of about 80° C. or higher.
33. The composition of claim 19 , which, when stored at about room temperature or higher for at least about twelve months, has no significant loss of efficacy.
34. The composition of claim 19 , which, when stored at about 30° C. or higher for at least about two years, has no significant loss of efficacy.
35. The composition of claim 19 , which, when stored at about 50° C. or higher for at least about six months, has no significant loss of efficacy.
36. The composition of claim 19 , which, when stored at about 50° C. or higher for at least about twelve months, has no significant loss of efficacy.