Liquid viral formulations
Provided herein are liquid viral formulations useful for the stabilization and storage of viruses and methods of preparing these formulations. The liquid viral formulations described herein include a virus (e.g., a purified virus) and a non-viral composition including excipients and a liquid carrier. The formulations can be used, for example, to retain the infectivity or immunogenicity of viruses during periods of storage.
1. A viral formulation comprising:
(a) a purified virus; and
(b) a non-viral composition comprising:
(i) mannitol;
(ii) sorbitol in a concentration of less than 2.5% based on the weight of the non-viral composition;
(iii) histidine;
(iv) Mg 2+ ; and
(v) a liquid carrier,
wherein the non-viral composition, excluding the liquid carrier, is free of monovalent cationic salts and wherein the non-viral composition is provided in an amount effective to stabilize the purified virus.
2. The formulation of claim 1 , wherein the combined concentration of mannitol and sorbitol is less than 10% by weight based on the weight of the non-viral composition.
3. The formulation of claim 1 , wherein the non-viral composition further comprises a non-ionic surfactant.
4. The formulation of claim 3 , wherein the non-ionic surfactant is polysorbate 80.
5. The formulation of claim 1 , wherein the viral formulation is substantially free of trehalose or free of Zn 2+ .
6. The formulation of claim 1 , wherein the virus is an oncolytic virus, a non-enveloped virus, or a reovirus.
7. The formulation of claim 1 , wherein Mg 2+ is present as magnesium chloride.
8. The formulation of claim 1 , wherein the liquid carrier is an aqueous carrier.
9. The formulation of claim 1 , wherein the viral formulation is stable at a temperature at about ambient temperature.
10. The formulation of claim 1 , wherein the viral formulation is stable at a temperature of about 4° C. or lower for at least three months, at least six months, at least twelve months, or at least eighteen months.
11. The formulation of claim 1 , which is suitable for dilution before administration.
12. A method of making a viral formulation, comprising the steps of:
(a) providing a virus; and
(b) combining the virus with a non-viral composition comprising:
(i) mannitol;
(ii) sorbitol in a concentration of less than 2.5% based on the weight of the non-viral composition;
(iii) histidine;
(iv) Mg 2+ ; and
(v) a liquid carrier,
wherein the non-viral composition, excluding the liquid carrier, is free of monovalent cationic salts, and wherein the non-viral composition is provided in an amount effective to stabilize the purified virus to form a viral formulation.
13. The method of claim 12 , wherein the combined concentration of mannitol and sorbitol in the non-viral composition is less than 10% by weight based on the weight of the non-viral composition.
14. The method of claim 12 , further comprising adding a non-ionic surfactant to the non-viral composition.
15. The method of claim 14 , wherein the non-ionic surfactant is polysorbate 80.
16. The method of claim 12 , wherein the viral formulation is substantially free of trehalose or free of Zn 2+ .
17. The method of claim 12 , further comprising diluting the viral formulation for infusion.
18. The method of claim 12 , wherein the virus is an oncolytic virus, a non-enveloped virus, or a reovirus.
19. The method of claim 12 , wherein Mg 2+ is present as magnesium chloride.
20. The method of claim 12 , wherein the liquid carrier is an aqueous carrier.
21. A viral formulation prepared according to the method of claim 12 .
22. A method of preserving or stabilizing a virus, comprising:
preparing a viral formulation according to claim 1 ; and
storing the viral formulation.
23. The method of claim 22 , wherein the virus is stored at a temperature at or below ambient temperature.
24. The method of claim 22 , wherein the temperature is selected from the group consisting of ambient temperature, from 2° C. to 8° C., 4° C., −20° C., and from −60° C. to −80° C.
25. A method of preparing a non-aggregating viral formulation, comprising preparing a viral formulation according to claim 1 .
26. The method of claim 25 , wherein the formulation is suitable for administration by parenteral infusion or injection.
27. The formulation of claim 6 , wherein the reovirus is selected from the group consisting of a mammalian reovirus, a recombinant or reassorted reovirus, and IDAC #190907-01.
28. The formulation of claim 27 , wherein the mammalian reovirus is a human reovirus.
29. The formulation of claim 28 , wherein the human reovirus is a serotype 3 reovirus.
30. The formulation of claim 29 , wherein the serotype 3 reovirus is a Dearing strain serotype 3 reovirus.
31. The method of claim 18 , wherein the reovirus is selected from the group consisting of a mammalian reovirus, a recombinant or reassorted reovirus, and IDAC #190907-01.
32. The method of claim 31 , wherein the mammalian reovirus is a human reovirus.
33. The method of claim 32 , wherein the human reovirus is a serotype 3 reovirus.
34. The method of claim 33 , wherein the serotype 3 reovirus is a Dearing strain serotype 3 reovirus.
35. A non-viral composition for use in preserving or stabilizing a virus comprising:
(a) mannitol;
(b) sorbitol in a concentration of less than 2.5% based on the weight of the non-viral composition;
(c) histidine;
(d) Mg 2+ ; and
(e) a liquid carrier,
wherein the non-viral composition, excluding the liquid carrier, is free of monovalent cationic salts, and wherein the non-viral composition is provided in an amount effective to stabilize said virus.