Influenza vaccines including combinations of particulate adjuvants and immunopotentiators

Abstract

Influenza vaccines containing insoluble particulate adjuvants have been found to elicit an IgG response that is primarily a TH2 response (IgG1). This response can be shifted towards a TH1 response (IgG2a) by including immunopotentiators in the compositions. Thus the invention provides an immunogenic composition comprising: (i) an influenza virus antigen; (ii) an insoluble particulate adjuvant; and (iii) a immunopotentiator.

1 . An immunogenic composition comprising: (i) an influenza virus antigen; (ii) an insoluble particulate adjuvant; and (iii) an immunopotentiator which comprises a TLR7 agonist. 
     
     
         2 . The composition of  claim 1 , wherein the influenza virus antigen is inactivated virus. 
     
     
         3 . The composition of  claim 1 , wherein the influenza virus antigen comprises whole virus, split virus, or purified surface antigens. 
     
     
         4 . The composition of  claim 1 , wherein the influenza virus antigen is from a H1, H2, H3, H5, H7 or H9 influenza A virus subtype. 
     
     
         5 . The composition of  claim 1 , wherein the influenza virus antigen is prepared from an influenza virus grown on cell culture. 
     
     
         6 . The composition of  claim 1 , wherein the influenza virus antigen is prepared from an influenza virus grown on eggs. 
     
     
         7 . The composition of  claim 1 , wherein the composition is free from ovalbumin, ovomucoid and chicken DNA. 
     
     
         8 . The composition of  claim 5 , wherein the composition contains less than 10 ng of cellular DNA from the cell culture host. 
     
     
         9 . The composition of  claim 5 , wherein the composition contains less than 10 ng of DNA that is 100 nucleotides or longer. 
     
     
         10 . The composition of  claim 1 , wherein the composition contains between 0.1 and 20 μg of haemagglutinin per viral strain. 
     
     
         11 . The composition of  claim 1 , wherein the insoluble particulate adjuvant is selected from the group consisting of: an aluminum salt; a calcium salt; and a microparticle. 
     
     
         12 . The composition of  claim 1 , wherein the insoluble particulate adjuvant comprises an aluminum hydroxide. 
     
     
         13 . The composition of  claim 1 , wherein the insoluble particulate adjuvant comprises an aluminum phosphate. 
     
     
         14 . The composition of  claim 1 , wherein the insoluble particulate adjuvant comprises a calcium phosphate. 
     
     
         15 . The composition of  claim 1 , wherein the insoluble particulate adjuvant comprises a microparticle made from poly(lactide-co-glycolide). 
     
     
         16 . The composition of  claim 1 , wherein the TLR7 agonist is imidazoquinoline. 
     
     
         17 - 18 . (canceled) 
     
     
         19 . A method for preparing an immunogenic composition comprising combining: (i) an influenza virus antigen; (ii) an insoluble particulate adjuvant; and (iii) an immunopotentiator comprising a TLR7 agonist. 
     
     
         20 . A kit comprising: (i) a first kit component comprising an influenza virus antigen; and (ii) a second kit component comprising an insoluble particulate adjuvant, wherein either (a) the first component or the second component includes an immunopotentiator comprising a TLR7 agonist, or (b) the kit includes a third kit component comprising an immunopotentiator comprising a TLR7 agonist. 
     
     
         21 . A method for inducing an immune response against an influenza virus in a subject comprising administering to the subject an immunogenic composition comprising: (i) an influenza virus antigen; (ii) an insoluble particulate adjuvant; and (iii) an immunopotentiator comprising a TLR7 agonist.