Polyanionic polymer adjuvants for haemophilus influenzae b saccharide vaccines

Abstract

The present invention relates to immunogenic compositions comprising capsular polysaccharide or oligosaccharide of H. influenzae B (PRP) and methods of making such compositions.

1 . An immunogenic composition comprising capsular polysaccharide or oligosaccharide of  Haemophilus influenzae  B (PRP) and a polyanionic polymer. 
     
     
         2 . The immunogenic composition of  claim 1 , wherein PRP is conjugated to a carrier protein which is a source of T-helper cell epitopes. 
     
     
         3 . The immunogenic composition of  claim 2 , wherein the carrier protein is selected from the group consisting of: tetanus toxoid, diphtheria toxoid, CRM197, and protein D. 
     
     
         4 . The immunogenic composition of  claim 1 , wherein the polyanionic polymer has anionic constitutional repeating units. 
     
     
         5 . The immunogenic composition of  claim 4 , wherein the polyanionic polymer comprises anionic constitutional repeating units obtained from a group consisting of: acrylic acid, methacrylic acid, maleic acid, fumaric acid, ethylsulphonic acid, vinylsulphonic acid, vinylsulphonic acid, styrenesulphonic acid, vinylphenylsulphuric acid, 2-methacryloyloxyethane sulphonic acid, 3-methacryloyloxy-2-hydroxypropanesulphonic acid, 3-methacryl amido-3-methylbutanoic acid, acrylamidomethylpropanesulfonic acid, vinylphosphoric acid, 4-vinylbenzoic acid, 3-vinyl oxypropane-1-sulphonic acid, N-vinylsuccinimidic acid, and salts of the foregoing. 
     
     
         6 . The immunogenic composition of  claim 1 , wherein the polyanionic polymer is an oligo- or poly-saccharide such as dextran. 
     
     
         7 . The immunogenic composition of  claim 1 , wherein the polyanionic polymer is an oligo- or poly-peptide and comprises anionic constitutional repeating units obtained from a group consisting of: L-aspartic acid, D-aspartic acid, L-glutamic acid, D-glutamic acid, and salts of the foregoing. 
     
     
         8 . The immunogenic composition of  claim 1 , wherein the polyanionic polymer is a polyanionic heteropolymer. 
     
     
         9 . The immunogenic composition of  claim 8 , wherein the polyanionic heteropolymer consists of two distinct anionic constitutional repeating units. 
     
     
         10 . The immunogenic composition of  claim 1 , wherein the polyanionic polymer is a polyanionic homopolymer. 
     
     
         11 . The immunogenic composition of  claim 1 , wherein the immunogenic composition comprises one or more further antigens. 
     
     
         12 . The immunogenic composition of  claim 11 , wherein the one or more further antigens comprise tetanus toxoid, diphtheria toxoid, and inactivated whole-cell  B. pertussis  or one or more acellular  B. pertussis  antigens. 
     
     
         13 . The immunogenic composition of  claim 11 , wherein the one or more further antigens comprise one or more acellular  B. pertussis  antigens selected from the group consisting of: pertussis toxiod, FHA, pertactin, agglutinogen 2 and agglutinogen 3. 
     
     
         14 . The immunogenic composition of  claim 11 , wherein the one or more further antigens comprise either or both of Inactivated Polio Vaccine (IPV) and Hepatitis B surface antigen, wherein Hepatitis B surface antigen is preferably adsorbed onto aluminium phosphate. 
     
     
         15 . The immunogenic composition of  claim 11 , which further comprises an adjuvant with a zero point charge greater than 8; wherein the polyanionic polymer prevents flocculation between the adjuvant and PRP and/or reduces the immunological interference that the adjuvant has on PRP. 
     
     
         16 . The immunogenic composition of  claim 15 , wherein the adjuvant is selected from the group consisting of: alum and aluminium hydroxide. 
     
     
         17 . A method to reduce the immunological interference of a  Haemophilus influenzae  B capsular polysaccharide or oligosaccharide (PRP), preferably conjugated, in a combination vaccine comprising one or more further antigens adsorbed to an adjuvant with a zero point charge greater than 8, wherein such method comprises the steps of:
 (i) adsorbing the one or more further antigens onto the adjuvant; and   (ii) adding an immunogenic composition comprising PRP and a polyanionic polymer to said one or more further antigens.   
     
     
         18 . A kit comprising: i) a first immunogenic composition comprising a  Haemophilus influenzae  B capsular polysaccharide or oligosaccharide (PRP), preferably conjugated, and a polyanionic polymer; and ii) a second immunogenic composition comprising one or more antigens adsorbed onto an adjuvant with a zero point charge greater than 8. 
     
     
         19 . The kit of  claim 18 , wherein the adjuvant is aluminium hydroxide. 
     
     
         20 . The kit of  claim 18 , wherein the second immunogenic composition comprises one or more antigens selected from a group consisting of: diphtheria toxoid, tetanus toxoid, pertussis toxoid, FHA and pertactin.