preparation of influenza virus vaccine antigens

Abstract

A number of improvements for preparing vaccine antigens from disintegrated influenza viruses are disclosed. A splitting step can be followed by detergent exchange. Splitting can take place in the presence of a buffer with a higher ionic strength and/or in the presence of phosphate buffer.

1 . A process for disrupting influenza virions, comprising steps of: (i) obtaining a composition comprising influenza virions in the absence of detergent; (ii) inactivating the influenza virions in the absence of detergent; (iii) splitting the inactivated virions with a reagent comprising a first detergent; and (iv) exchanging the first detergent for a second detergent. 
     
     
         2 . A process for disrupting influenza virions, comprising steps of: (i) obtaining a composition comprising influenza virions; (ii) splitting the virions by exposure to a detergent in a buffer having an ionic strength of 100 mM or greater. 
     
     
         3 . A process for disrupting influenza virions, comprising steps of: (i) obtaining a composition comprising influenza virions in the presence of a phosphate buffer; (ii) inactivating the influenza virions in the presence of a phosphate buffer; and (iii) splitting the inactivated virions in the presence of a phosphate buffer. 
     
     
         4 . A process for preparing an influenza vaccine, wherein (a) a hemagglutinin-containing antigen preparation is obtained from a virus by a process in which influenza virions are disrupted by the process of  claim 3 , and (b) the hemagglutinin-containing antigen preparation is used to prepare the vaccine. 
     
     
         5 . The process of  claim 3 , wherein the influenza virions are from an influenza A virus. 
     
     
         6 . The process of  claim 3 , wherein the influenza virions are from an influenza A virus of H5 hemagglutinin subtype. 
     
     
         7 . The process of  claim 3 , wherein the influenza virions are prepared from eggs. 
     
     
         8 . The process of  claim 3 , wherein the influenza virions are prepared from mammalian cell culture. 
     
     
         9 . The process of  claim 4 , wherein the vaccine contains hemagglutinin at 7.5 μg per strain. 
     
     
         10 . The process of  claim 4 , wherein the vaccine contains an adjuvant. 
     
     
         11 . The process of  claim 10 , wherein the adjuvant comprises an oil-in-water emulsion. 
     
     
         12 . A method of raising an immune response in a patient, comprising the step of administering a vaccine prepared by the process of  claim 4 .