Refrigerator-temperature stable influenza vaccine compositions

Abstract

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 . (canceled)  
   
   
       3 . (canceled)  
   
   
       4 . A refrigerator stable influenza virus composition produced by the method of  claim 1 .  
   
   
       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 . (canceled)  
   
   
       13 . A vaccine comprising the immunogenic composition of  claim 11 .  
   
   
       14 - 17 . (canceled)  
   
   
       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 . (canceled)  
   
   
       20 . The refrigerator stable immunogenic composition of  claim 18  comprising three influenza virus strains.  
   
   
       21 . A vaccine comprising the refrigerator stable immunogenic composition of  claim 18  or  20 .