Adjuvanted Influenza Vaccines for Pediatric Use

Abstract

An influenza vaccine adjuvanted with a sub-micron oil-in-water emulsion elicits significantly higher immune responses in human pediatric populations. Compared to an existing unadjuvanted pediatric influenza vaccine, the adjuvanted vaccines provided herein can induce in children a longer persistence of high serum antibody titers and also longer seroconversion and seroprotection. The improvement in immune responses is seen for both influenza A virus and influenza B virus strains, but it is particularly marked for influenza B virus. Moreover, while the existing vaccine provides poor immunity in children after a single dose, the adjuvanted vaccine provides high seroprotection rates against the influenza A virus H3N2 subtype even after a single dose. Furthermore, the adjuvanted vaccine offers significantly better seroprotection against mismatched strains of influenza A virus.

1 - 2 . (canceled) 
     
     
         3 : A composition in unit dosage form, wherein: the composition comprises (i) an influenza B virus strain antigen; (ii) an influenza A virus strain antigen; and (iii) an adjuvant; and the unit dosage has a volume of less than 0.5 mL and contains between 6-9 μg of hemagglutinin per influenza virus strain, wherein the adjuvant comprises an oil-in-water emulsion in which the majority of oil droplets have a diameter of less than 1 μm and the oil droplets comprise squalene; and wherein the composition is immunogenic in that when administered to a pediatric population of at least 50 children between 6 and 36 months of age, the composition will elicit efficacy that satisfies one or more of the following criteria: (a) ≧70% seroprotection; (b) ≧40% seroconversion or significant increase; and/or (c) a geometric mean titer increase of ≧2.5-fold. 
     
     
         4 : A kit for preparing an immunogenic composition for use in immunizing a child between 6 and 36 months of age, wherein the kit comprises (i) a first kit component comprising an influenza B virus strain antigen and an influenza A virus strain antigen and (ii) a second kit component comprising an adjuvant, wherein the adjuvant comprises an oil-in-water emulsion in which the majority of oil droplets have a diameter of less than 1 μm and the oil droplets comprise squalene; and wherein the immunogenic composition, has a unit dose of between 0.2 mL and 0.45 mL, and contains between 6-9 μg of hemagglutinin per influenza virus strain. 
     
     
         5 : A method for raising an immune response to an influenza B virus strain in a human child of up to 72 months of age, comprising a step of administering to the child an immunogenic composition in unit dosage form comprising: (i) an influenza B virus strain antigen; (ii) an influenza A virus strain antigen; and (iii) an adjuvant, wherein the adjuvant comprises an oil-in-water emulsion in which the majority of oil droplets have a diameter of less than 1 μm and the oil droplets comprise squalene; and wherein the unit dosage has a volume of less than 0.5 mL and contains between 6-9 μg of hemagglutinin per influenza virus strain. 
     
     
         6 : The composition of  claim 3 , wherein the unit dosage is between 0.2 mL and 0.3 mL. 
     
     
         7 : The composition of  claim 6 , wherein the composition includes a subtype H1N1 influenza A strain antigen and a subtype H3N2 influenza A strain antigen. 
     
     
         8 : The composition of  claim 7 , wherein the oil-in-water emulsion further comprises polysorbate 80. 
     
     
         9 : The composition of  claim 8 , wherein the oil-in-water emulsion further comprises α-tocopherol. 
     
     
         10 : The composition of  claim 9 , wherein the composition is a split virion or purified surface antigen vaccine. 
     
     
         11 : The composition of  claim 10 , wherein the unit dosage of the composition contains between 7 and 8 μg of hemagglutinin per influenza virus strain. 
     
     
         12 : The composition of  claim 3 , wherein the composition is a split virion or purified surface antigen vaccine, or wherein the antigen is in the form of a virosome. 
     
     
         13 : The composition of  claim 3 , wherein the composition includes a subtype H1N1 influenza A strain antigen and a subtype H3N2 influenza A strain antigen. 
     
     
         14 : The composition of  claim 3 , wherein the composition comprises hemagglutinin from: (i) an A/H1N1 strain; (ii) an A/H3N2 strain; (iii) a B/Victoria/2/87-like strain; and (iv) a B/Yamagata/16/88-like strain. 
     
     
         15 : The kit of  claim 4 , wherein the unit dosage is between 0.2 mL and 0.3 mL. 
     
     
         16 : The method of  claim 5 , wherein the unit dosage is between 0.2 mL and 0.3 mL. 
     
     
         17 : The kit of  claim 15 , wherein the composition includes a subtype H1N1 influenza A strain antigen and a subtype H3N2 influenza A strain antigen. 
     
     
         18 : The method of  claim 16 , wherein the composition includes a subtype H1N1 influenza A strain antigen and a subtype H3N2 influenza A strain antigen. 
     
     
         19 : The kit of  claim 17 , wherein the oil-in-water emulsion further comprises polysorbate 80. 
     
     
         20 : The method of  claim 18 , wherein the oil-in-water emulsion further comprises polysorbate 80. 
     
     
         21 : The kit of  claim 19 , wherein the oil-in-water emulsion further comprises α-tocopherol. 
     
     
         22 : The method of  claim 20 , wherein the oil-in-water emulsion further comprises α-tocopherol. 
     
     
         23 : The kit of  claim 21 , wherein the composition is a split virion or purified surface antigen vaccine. 
     
     
         24 : The method of  claim 22 , wherein the composition is a split virion or purified surface antigen vaccine. 
     
     
         25 : The kit of  claim 23 , wherein the unit dosage of the composition contains between 7 and 8 μg of hemagglutinin per influenza virus strain. 
     
     
         26 : The method of  claim 24 , wherein the unit dosage of the composition contains between 7 and 8 μg of hemagglutinin per influenza virus strain. 
     
     
         27 : The kit of  claim 4 , wherein the composition is a split virion or purified surface antigen vaccine, or wherein the antigen is in the form of a virosome. 
     
     
         28 : The method of  claim 5 , wherein the composition is a split virion or purified surface antigen vaccine, or wherein the antigen is in the form of a virosome. 
     
     
         29 : The kit of  claim 4 , wherein the composition includes a subtype H1N1 influenza A strain antigen and a subtype H3N2 influenza A strain antigen. 
     
     
         30 : The method of  claim 5 , wherein the composition includes a subtype H1N1 influenza A strain antigen and a subtype H3N2 influenza A strain antigen. 
     
     
         31 : The kit of  claim 4 , wherein the composition comprises hemagglutinin from: (i) an A/H1N1 strain; (ii) an A/H3N2 strain; (iii) a B/Victoria/2/87-like strain; and (iv) a B/Yamagata/16/88-like strain. 
     
     
         32 : The method of  claim 5 , wherein the composition comprises hemagglutinin from: (i) an A/H1N1 strain; (ii) an A/H3N2 strain; (iii) a B/Victoria/2/87-like strain; and (iv) a B/Yamagata/16/88-like strain.