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) sucrose in a concentration of less than 4.5% based on the weight of the non-viral composition;
(ii) Mg 2+ ;
(iii) a non-ionic surfactant; and
(iv) a liquid carrier,
wherein the non-viral composition is free of non-sucrose polyols, and carboxylates;
wherein monovalent cationic salts are not present in the non-viral composition as excipients contributing to the stability of the virus; and
wherein the non-viral composition is provided in an amount effective to stabilize the purified virus.
2. The viral formulation of claim 1 , wherein the non-viral composition further comprises a non-ionic surfactant.
3. The viral formulation of claim 2 , wherein the non-ionic surfactant is polysorbate 80.
4. The viral formulation of claim 1 , wherein the virus is an oncolytic virus, a non-enveloped virus, or a reovirus.
5. The viral formulation of claim 4 , wherein the reovirus is selected from the group consisting of a mammalian reovirus, a recombinant or reassorted reovirus, and IDAC #190907-01.
6. The viral formulation of claim 5 , wherein the mammalian reovirus is a human reovirus.
7. The viral formulation of claim 6 , wherein the human reovirus is a serotype 3 reovirus.
8. The viral formulation of claim 7 , wherein the serotype 3 reovirus is a Dearing strain serotype 3 reovirus.
9. The viral formulation of claim 1 , wherein Mg 2+ is present as magnesium chloride.
10. The viral formulation of claim 1 , wherein the liquid carrier is an aqueous carrier.
11. The viral formulation of claim 1 , wherein the viral formulation is stable at a temperature at about ambient temperature.
12. The viral 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.
13. The viral formulation of claim 1 , wherein the viral formulation is suitable for dilution before administration.
14. A viral formulation, consisting essentially of:
(a) a purified virus; and
(b) a non-viral composition comprising:
(i) sucrose in a concentration of less than 4.5% based on the weight of the non-viral composition;
(ii) Mg 2+ ;
(iii) a non-ionic surfactant; and
(iv) a liquid carrier,
wherein monovalent cationic salts are not present in the non-viral composition as excipients contributing to the stability of the virus and wherein the non-viral composition is provided in an amount effective to stabilize the purified virus.
15. 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) sucrose in a concentration of less than 4.5% based on the weight of the non-viral composition;
(ii) Mg 2+ ;
(iii) a non-ionic surfactant; and
(iv) a liquid carrier,
wherein the non-viral composition is free of non-sucrose polyols, and carboxylates;
wherein monovalent cationic salts are not present in the non-viral composition as excipients contributing to the stability of the virus; and
wherein the non-viral composition is provided in an amount effective to stabilize the virus,
to form a viral formulation.
16. The method of claim 15 , further comprising adding a non-ionic surfactant to the non-viral composition.
17. The method of claim 16 , wherein the non-ionic surfactant is polysorbate 80.
18. The method of claim 15 , further comprising diluting the viral formulation for infusion.
19. The method of claim 15 , wherein the virus is an oncolytic virus, a non-enveloped virus, or a reovirus.
20. The method of claim 19 , wherein the reovirus is selected from the group consisting of a mammalian reovirus, a recombinant or reassorted reovirus, and IDAC #190907-01.
21. The method of claim 20 , wherein the mammalian reovirus is a human reovirus.
22. The method of claim 21 , wherein the human reovirus is a serotype 3 reovirus.
23. The method of claim 22 , wherein the serotype 3 reovirus is a Dearing strain serotype 3 reovirus.
24. The method of claim 15 , wherein Mg 2+ is present as magnesium chloride.
25. The method of claim 15 , wherein the liquid carrier is an aqueous carrier.
26. A viral formulation prepared according to the method of claim 15 .
27. 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 consisting essentially of:
(i) sucrose in a concentration of less than 4.5% based on the weight of the non-viral composition;
(ii) Mg 2+ ;
(iii) a non-ionic surfactant; and
(iv) a liquid carrier,
wherein monovalent cationic salts are not present in the non-viral composition as excipients contributing to the stability of the virus and wherein the non-viral composition is provided in an amount effective to stabilize the virus,
to form a viral formulation.
28. A method of preserving or stabilizing a virus, comprising:
preparing the viral formulation of claim 1 ; and
storing the viral formulation.
29. The method of claim 28 , wherein the virus is stored at a temperature at or below ambient temperature.
30. The method of claim 29 , 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.
31. A viral formulation of claim 1 , wherein the viral formulation is non-aggregating.
32. The viral formulation of claim 31 , wherein the viral formulation is suitable for administration by parenteral infusion or injection.