REFRIGERATOR-TEMPERATURE STABLE INFLUENZA VACCINE COMPOSITIONS
Methods and compositions for the optimization and production of refrigerator-temperature stable virus, e.g., influenza, compositions are provided. Formulations and immunogenic compositions comprising refrigerator-temperature stable virus compositions are provided.
1 . A method of making a refrigerator stable influenza virus composition, the method comprising: infection of a population of host eggs or into a population of host cells with influenza viruses; culturing the population of host eggs or population of host cells at an appropriate temperature; recovering influenza viruses in a viral harvest; clarifying the viral harvest by filtration, thereby producing a clarified viral harvest; subjecting the clarified viral harvest to continuous flow centrifugation, thereby producing a further clarified viral harvest; and sterilizing said further clarified viral harvest by filtration.
2 . The method of claim 1 , wherein the influenza viruses comprise one or more of: an attenuated influenza virus, a cold-adapted influenza virus, a temperature-sensitive influenza virus, or an attenuated cold-adapted temperature-sensitive influenza virus.
3 . The method of claim 1 , wherein the influenza viruses comprise one or more influenza A virus strains and/or one or more influenza B virus strains.
4 . A refrigerator stable influenza virus composition produced by the method of claim 1 , 2 , or 3 .
5 . A refrigerator stable influenza virus composition which comprises at least one strain of influenza virus and one or more members selected from the group consisting of:
a) 6-8% sucrose
b) 1-2% arginine monohydrochloride;
c) 0.05-0.1% glutamic acid, monosodium monohydrate; and
d) 0.5-2% gelatin hydrolysate.
6 . The refrigerator stable influenza virus composition of claim 5 , which comprises 6.84% sucrose, 1.21% arginine monohydrochloride, 0.094% glutamic acid, monosodium monohydrate; and 1% gelatin hydrolysate.
7 . The refrigerator stable influenza virus composition of claim 4 , wherein said composition has a potency loss of less than 1.0 logs when stored at 4° C. for at least 3 months.
8 . The refrigerator stable influenza virus composition of claim 5 , 6 , or 7 , wherein said composition has a potency loss of less than 1.0 logs when stored at 4° C. for at least 3 months.
9 . The refrigerator stable influenza virus composition of claim 8 , wherein said composition further comprises a cold adapted temperature-sensitive attenuated influenza virus.
10 . An immunogenic composition comprising the refrigerator stable influenza virus composition of claim 7 .
11 . An immunogenic composition comprising the refrigerator stable influenza virus composition of claim 9 .
12 . A vaccine comprising the immunogenic composition of claim 10 .
13 . A vaccine comprising the immunogenic composition of claim 11 .
14 . The method of claim 1 , wherein the influenza viruses comprise a genetic backbone of one or more of the following influenza viruses: A/Ann Arbor/6/60 and B/Ann Arbor/1/66.
15 . A refrigerator stable influenza virus composition produced by the method of claim 14 .
16 . An immunogenic composition comprising the refrigerator stable influenza virus composition of claim 15 .
17 . A vaccine comprising the immunogenic composition of claim 16 .
18 . A refrigerator stable immunogenic composition comprising at least one live influenza virus, wherein the composition has a potency loss of less than 1.0 logs when stored for a period of 3 months at 4-8° C.
19 . The refrigerator stable immunogenic composition of claim 18 , wherein the composition has a potency loss of less than 1.0 logs when stored for a period of 12 months at 4-8° C.
20 . The refrigerator stable immunogenic composition of claim 18 comprising three influenza virus strains.
21 . The refrigerator stable immunogenic composition of claim 19 comprising three influenza virus strains.
22 . A vaccine comprising the refrigerator stable immunogenic composition of claim 18 .
23 . A vaccine comprising the refrigerator stable immunogenic composition of claim 19 .
24 . A vaccine comprising the refrigerator stable immunogenic composition of claim 20 .
25 . A vaccine comprising the refrigerator stable immunogenic composition of claim 21 .