Methods of producing influenza vaccine compositions
Methods and compositions for the optimization of production of influenza viruses suitable as influenza vaccines are provided.
1. A liquid refrigerator-stable live influenza virus composition, comprising:
(a) one or more purified live influenza viruses;
(b) less than 5% (v/v) normal allantoic fluid; and
(c) a stabilizer consisting of:
(i) sucrose, potassium phosphate and glutamate (SPG),
(ii) 1% (w/v) to 5% (w/v) arginine, and
(iii) 1% (w/v) to 4% (w/v) gelatin,
wherein the composition when stored from 2° C. to 8° C. exhibits less than or equal to a 1.0 log potency loss in 6 months or less than or equal to a 0.080 log potency loss per month.
2. The liquid refrigerator-stable live influenza virus composition of claim 1 , wherein at least one influenza virus is selected from: an attenuated influenza virus, a cold-adapted influenza virus, a temperature-sensitive influenza virus, an attenuated temperature-sensitive influenza virus, an attenuated cold-adapted influenza virus, a temperature-sensitive cold-adapted influenza virus, and an attenuated cold-adapted temperature-sensitive influenza virus.
3. The liquid refrigerator-stable live influenza virus composition claim 1 , wherein the composition is substantially free of normal allantoic fluid.
4. The liquid refrigerator-stable live influenza virus composition of claim 1 , wherein the stabilizer comprises from 1% (w/v) to 2% (w/v) arginine.
5. The liquid refrigerator-stable live influenza virus composition of claim 1 , wherein the stabilizer comprises 1% (w/v) gelatin.
6. The liquid refrigerator-stable live influenza virus composition of claim 1 , wherein the stabilizer comprises from 7% (w/v) to 10% (w/v) sucrose.
7. The liquid refrigerator-stable live influenza virus composition of claim 1 , wherein the composition has a pH of 7.2.
8. The liquid refrigerator-stable live influenza virus composition of claim 1 , wherein the composition does not comprise EDTA.
9. The liquid refrigerator-stable live influenza virus composition of claim 1 , comprising three influenza virus strains.
10. The liquid refrigerator-stable live influenza virus composition of claim 1 , wherein the potency is measured in fluorescent focus units.
11. An immunogenic composition comprising the liquid refrigerator-stable live influenza virus composition of claim 1 .
12. A vaccine comprising the immunogenic composition of claim 11 .
13. The liquid refrigerator-stable live influenza virus composition of claim 1 , wherein the composition when stored from 2° C. to 8° C. exhibits less than or equal to a 1.0 log potency loss in 12 months.