Stable, spray dried, immunogenic, viral compositions
Viruses, and particularly genetically engineered, replication deficient viruses such as adenoviruses, poxviruses, MVA viruses, and baculoviruses which encode one or more antigens of interest, such as TB, malarial, and HIV antigens, are spray dried with a mannitol-cyclodextrin-trehalose-dextran (MCTD) to form a powder where the viability of the viruses are maintained at a suitable level for mass vaccinations after spray drying, and where the viability of the viruses are maintained at suitable level over a period of storage time, even in the presence of humidity.
1. An immunogenic composition having low hygroscopicity, comprising:
one or more live viruses in a powder formulation spray dried from a composition comprising mannitol at 10-150 mg/ml, cyclodextrin at 0.1-10 mg/ml, trehalose at 0.2-30 mg/ml, and dextran at 0.1-30 mg/ml, wherein the moisture content is less than 5%.
2. The immunogenic composition of claim 1 wherein said powder formulation is spray dried from a composition which comprises mannitol at 50-100 mg/ml, cyclodextrin at 0.2-1 mg/ml, trehalose at 0.5-5 mg/ml, and dextran at 0.5-5 mg/ml.
3. The immunogenic composition of claim 1 wherein said cyclodextrin includes one or more of α- or β- or γ-cyclodextrin.
4. The immunogenic composition of claim 1 wherein said dextran has a molecular weight ranging from 25K to 500 K.
5. The immunogenic composition of claim 4 wherein said dextran has molecular weight ranging from 40K to 90 K.
6. The immunogenic composition of claim 1 further comprising buffering agents.
7. The immunogenic composition of claim 1 wherein said one or more viruses includes at least one virus that is a genetically engineered viral vaccine vector encoding one or more passenger genes that are foreign to said genetically engineered viral vaccine vector.
8. The immunogenic composition of claim 7 wherein said viral vaccine vector is non-replicating or replication deficient.
9. The immunogenic composition of claim 7 wherein said viral vaccine vector is an adenovirus.
10. The immunogenic composition of claim 7 wherein said viral vaccine vector includes nucleic acid sequences that encode one or more proteins that interfere with mammalian host cell type I interferon (IFN) responses.
11. The immunogenic composition of claim 7 wherein said viral vaccine vector expresses one or more viral, bacterial or parasitic antigens from said one or more passenger genes.
12. The immunogenic composition of claim 7 wherein said one or more passenger genes express one or more tuberculosis antigens.
13. The immunogenic composition of claim 7 wherein said one or more passenger genes express one or more malarial antigens.
14. The immunogenic composition of claim 7 wherein said one or more passenger genes express one or more HIV antigens.
15. The immunogenic composition of claim 1 wherein said powder formulation has a median volume diameter of 3.2-3.5 μm.
16. A method of forming an immunogenic composition having low hygroscopicity, comprising:
spray drying one or more live viruses from a composition comprising mannitol at 10-150 mg/ml, cyclodextrin at 0.1-10 mg/ml, trehalose at 0.2-30 mg/ml, and dextran at 0.1-30 mg/ml to form a spray dried powder containing said one or more live viruses, wherein the moisture content is less than 5%.
17. The method of claim 16 wherein said one or more viruses includes at least one virus that is a genetically engineered viral vaccine vector encoding one or more passenger genes that are foreign to said genetically engineered viral vaccine vector.
18. The method of claim 17 wherein said viral vaccine vector is non-replicating or replication deficient.
19. The method of claim 17 wherein said viral vaccine vector is an adenovirus.
20. The method of claim 17 wherein said viral vaccine vector expresses one or more viral, bacterial or parasitic antigens from said one or more passenger genes.
21. The method of claim 17 wherein said one or more passenger genes express one or more tuberculosis antigens, malarial antigens, or HIV antigens.
22. An immunogenic composition having low hygroscopicity, consisting essentially of one or more live viruses in a powder formulation spray dried from a composition comprising mannitol at 10-150 mg/ml, cyclodextrin at 0.1-10 mg/ml, trehalose at 0.2-30 mg/ml, and dextran at 0.1-30 mg/ml.
23. The immunogenic composition of claim 1 , wherein the immunogenic composition has lower hygroscopicity than an immunogenic composition comprising one or more live viruses in a powder formulation spray dried from a composition consisting of trehalose or dextran.
24. The immunogenic composition of claim 1 , wherein the immunogenic composition is hydrophobic.