Enhanced thermal stability for adenoviral vectors through spray drying

1. An adenovirus composition comprising adenovirus particles and an excipient, wherein the excipient comprises a mixture of dextran and mannitol in amounts effective to maintain at least 40% of the adenovirus activity after spray drying,

wherein the excipient comprises about 60 wt % to about 75 wt % of the mannitol and/or the excipient comprises about 25 wt % to about 40 wt % dextran.

2. The adenovirus composition of claim 1 , wherein the adenovirus is a recombinant DNA adenovirus.

3. The adenovirus composition of claim 1 , wherein the excipient comprises a mixture of dextran and mannitol in amounts effective to maintain at least 50% of the adenovirus activity after spray drying.

4. The adenovirus composition of claim 1 , wherein the excipient comprises a mixture of dextran and mannitol in amounts effective to maintain at least 40% of the adenovirus activity after spray drying and storage at 20° C., less than 10% relative humidity (RH) and for at least 90 days.

5. The adenovirus composition of claim 1 , further comprising a pharmaceutically acceptable carrier.

6. The adenovirus composition of claim 1 , which has been spray dried.

7. The adenovirus composition of claim 1 , wherein the change in adenovirus infectivity following spray drying and storage at 20° C., <10% RH and for 90 days is less than 1.0 log unit.

8. A method for preparing the adenovirus composition of claim 1 comprising:

a) combining the adenovirus with an aqueous solution comprising an excipient, wherein the excipient comprises a mixture of dextran and mannitol in amounts effective to maintain at least 40% of the adenovirus activity after spray drying to provide a mixture; and

b) spray drying the mixture to provide the adenovirus composition.

9. The method of claim 8 , wherein the aqueous solution comprising the excipient is prepared by dissolving the dextran and mannitol in an aqueous solution at a concentration in the range of about 0.1 mg excipient per mL of water to about 10 mg excipient per mL of water.

10. The method of claim 8 , wherein the aqueous solution comprising the excipient has a pH of about 6 to about 7.

11. The method of claim 8 , wherein the excipient comprises a mixture of dextran and mannitol in amounts effective to maintain at least 30% of the adenovirus activity after spray drying and storage at 20° C., less than 10% RH and for at least 90 days.

12. The method of claim 8 , wherein the excipient comprises about 60 wt % to about 75 wt % of the mannitol.

13. The method of claim 8 , wherein the excipient comprises about 25 wt % to about 40 wt % dextran.

14. The method of claim 8 , wherein the change in adenovirus infectivity following spray drying and storage at 20° C., <10% RH and for 90 days is less than 1.0 log unit.

15. The method of claim 8 , further comprising the step of processing the stabilized adenovirus composition into a formulation suitable for administration as a liquid injection, or processing the stabilized adenovirus composition into a formulation suitable for administration via ingestion, inhalation or via pulmonary delivery.

16. A stabilized spray dried adenovirus composition prepared using the method of claim 8 .

17. A method for delivering or transferring one or more nucleic acid sequences to target cells comprising administering an effective amount of an adenovirus composition of claim 1 to the cells.

18. A method for treating a subject with a vaccine comprising administering an effective amount of an adenovirus composition of claim 1 to a subject in need thereof.

19. A method for gene therapy comprising administering an effective amount of an adenovirus composition of claim 1 to a subject in need thereof.