Combination vaccines with lower doses of antigen and/or adjuvant

Abstract

Combination vaccine compositions as well as methods for their manufacture have a relatively low amount of antigen and/or a relatively low amount of aluminium, but they can nevertheless have immunogenicity which is comparable to combination vaccines with a relatively high amount of antigen and/or a relatively high amount of aluminium. Aluminium-free combination vaccine compositions are also provided e.g. compositions which are adjuvanted with an oil-in-water emulsion adjuvant.

1 . An immunogenic composition in a unit dose form for administration to a patient comprising (i) a diphtheria toxoid, a tetanus toxoid, and an acellular  pertussis  antigen which contains a  pertussis  toxoid, (ii) an aluminium salt adjuvant, wherein the amount of Al +++  in the unit dose is less than 0.2 mg, and (iii) a TLR agonist adsorbed to the aluminium salt adjuvant. 
     
     
         2 . (canceled) 
     
     
         3 . The composition of  claim 1 , wherein the composition includes one or more of (i) a Hib conjugate, (ii) a hepatitis B virus surface antigen, and/or (iii) an inactivated poliovirus antigen. 
     
     
         4 . (canceled) 
     
     
         5 . An immunogenic composition in a unit dose form for administration to a patient comprising (i) a low dose of each of a diphtheria toxoid, a tetanus toxoid, and a  pertussis  toxoid, (ii) an aluminium salt adjuvant, wherein the amount of Al +++  in the unit dose is less than 0.2 mg, and (iii) a TLR agonist adsorbed to the aluminium salt adjuvant. 
     
     
         6 . (canceled) 
     
     
         7 . The composition of any one of  claim 5 , wherein the composition has ≦8 Lf/ml diphtheria toxoid. 
     
     
         8 . The composition of any one of  claim 5 , wherein the composition has ≦3.5 Lf/ml tetanus toxoid. 
     
     
         9 . The composition of any one of  claim 5 , wherein the acellular  pertussis  antigen has ≦5 μg/ml  pertussis  toxoid. 
     
     
         10 . The composition of any one of  claim 5 , wherein the composition comprises a low dose of a Hib conjugate. 
     
     
         11 . The composition of  claim 10 , wherein the composition has ≦5 μg/ml Hib saccharide. 
     
     
         12 . The composition of any one of  claim 5 , wherein the composition comprises a low dose of HBsAg. 
     
     
         13 . The composition of  claim 12 , wherein the composition has ≦5 μg/mlHBsAg. 
     
     
         14 . The composition of any one of  claim 5 , wherein the composition comprises a low dose of inactivated poliovirus. 
     
     
         15 . The composition of  claim 14 , wherein the composition has (i) ≦20 DU/ml type 1 poliovirus and/or (ii) ≦4 DU/ml type 2 poliovirus and/or (iii) ≦16 DU/ml type 3 poliovirus. 
     
     
         16 . The composition of  claim 5 , wherein the aluminium salt adjuvant is (i) an aluminium hydroxide adjuvant or (ii) an aluminium phosphate adjuvant or (iii) a mixture of an aluminium hydroxide adjuvant and an aluminium phosphate adjuvant. 
     
     
         17 . The composition of  claim 5 , including an aluminium hydroxide adjuvant to which a TLR7 agonist is adsorbed (e.g. ‘compound T’). 
     
     
         18 . An immunogenic composition comprising (i) an oil-in-water emulsion adjuvant (ii) a diphtheria toxoid, a tetanus toxoid, a  pertussis  toxoid, and a Hib conjugate (iii) a hepatitis B virus surface antigen and/or an inactivated poliovirus antigen. 
     
     
         19 . The composition of  claim 18 , wherein the composition is aluminium-free. 
     
     
         20 . The composition of  claim 18 , wherein the oil-in-water emulsion adjuvant has oil droplets with a sub-micron diameter. 
     
     
         21 . The composition of  claim 18 , wherein the oil-in-water emulsion adjuvant includes squalene and/or polysorbate 80. 
     
     
         22 . The composition of  claim 18 , including conjugated capsular saccharide from one or more of meningococcal serogroups A, C, W135 and/or Y. 
     
     
         23 . The composition of  claim 18 , including conjugated capsular saccharide from one or more of pneumococcal serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and/or 33F. 
     
     
         24 . The composition of  claim 18 , including (i) a meningococcal factor H binding protein antigen and/or (ii) a Neisserial Heparin Binding Antigen and/or (iii) a meningococcal NhhA antigen and/pr (iv) a meningococcal outer membrane vesicle. 
     
     
         25 . (canceled)