Multivalent pneumococcal polysaccharide-protein conjugate composition

Abstract

An immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection.

1 . A multivalent immunogenic composition, comprising: 13 distinct polysaccharide-protein conjugates, together with a physiologically acceptable vehicle, wherein each of the conjugates comprises a capsular polysaccharide from a different serotype of  Streptococcus pneumoniae  conjugated to a carrier protein, and the capsular polysaccharides are prepared from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.  
     
     
         2 . The immunogenic composition of  claim 1 , wherein the carrier protein is CRM 197 .  
     
     
         3 . The immunogenic composition of  claim 1 , further comprising an adjuvant.  
     
     
         4 . The immunogenic composition  claim 3 , wherein the adjuvant is an aluminum-based adjuvant.  
     
     
         5 . The immunogenic composition of  claim 4 , wherein the adjuvant is selected from the group consisting of aluminum phosphate, aluminum sulfate and aluminum hydroxide.  
     
     
         6 . The immunogenic composition of  claim 5 , wherein the adjuvant is aluminum phosphate.  
     
     
         7 . A method of inducing an immune response to a  Streptococcus pneumoniae  capsular polysaccharide conjugate, comprising administering to a human an immunologically effective amount of the immunogenic composition of  claim 1 .  
     
     
         8 . The method of  claim 7 , wherein the immunogenic composition administered is a single 0.5 mL dose formulated to contain: 2 μg of each saccharide, except for 6B at 4 μg; approximately 29 μg CRM 197  carrier protein; 0.125 mg of elemental aluminum (0.5 mg aluminum phosphate) adjuvant; and sodium chloride and sodium succinate buffer as excipients.  
     
     
         9 . A multivalent immunogenic composition, comprising polysaccharide-protein conjugates together with a physiologically acceptable vehicle, wherein each of the conjugates comprises a capsular polysaccharide from a different serotype of  Streptococcus pneumoniae  conjugated to a carrier protein, and the capsular polysaccharides are prepared from serotype 3 and at least one additional serotype.  
     
     
         10 . The immunogenic composition of  claim 9 , wherein the additional serotype is selected from the group consisting of serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.  
     
     
         11 . The immunogenic composition of  claim 9 , wherein the carrier protein is CRM 197 .  
     
     
         12 . The immunogenic composition of  claim 9 , further comprising an adjuvant.  
     
     
         13 . The immunogenic composition  claim 12 , wherein the adjuvant is an aluminum-based adjuvant.  
     
     
         14 . The immunogenic composition of  claim 13 , wherein the adjuvant is selected from the group consisting of aluminum phosphate, aluminum sulfate and aluminum hydroxide.  
     
     
         15 . The immunogenic composition of  claim 14 , wherein the adjuvant is aluminum phosphate.  
     
     
         16 . A method of inducing an immune response to a  Streptococcus pneumoniae  capsular polysaccharide conjugate, comprising administering to a human an immunologically effective amount of the immunogenic composition of  claim 9 .  
     
     
         17 . The method of  claim 16 , wherein the immunogenic composition administered is a single 0.5 mL dose formulated to contain: 2 μg of each saccharide, except for 6B at 4 μg; approximately 29 μg CRM 197  carrier protein; 0.125 mg of elemental aluminum (0.5 mg aluminum phosphate) adjuvant; and sodium chloride and sodium succinate buffer as excipients.  
     
     
         18 . A multivalent immunogenic composition, comprising polysaccharide-protein conjugates together with a physiologically acceptable vehicle, wherein each of the conjugates comprises a capsular polysaccharide from a different serotype of  Streptococcus pneumoniae  conjugated to a carrier protein, and the capsular polysaccharides are prepared from serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and at least one additional serotype.  
     
     
         19 . The immunogenic composition of  claim 18 , wherein said additional serotype is selected from the group consisting of serotypes 1, 3, 5, 6A, 7F, and 19A.  
     
     
         20 . The immunogenic composition of  claim 18 , wherein the carrier protein is CRM 197 .  
     
     
         21 . The immunogenic composition of  claim 18 , further comprising an adjuvant.  
     
     
         22 . The immunogenic composition  claim 21 , wherein the adjuvant is an aluminum-based adjuvant.  
     
     
         23 . The immunogenic composition of  claim 22 , wherein the adjuvant is selected from the group consisting of aluminum phosphate, aluminum sulfate and aluminum hydroxide.  
     
     
         24 . The immunogenic composition of  claim 23 , wherein the adjuvant is aluminum phosphate.  
     
     
         25 . A method of inducing an immune response to a  Streptococcus pneumoniae  capsular polysaccharide conjugate, comprising administering to a human an immunologically effective amount of the immunogenic composition of  claim 18 .  
     
     
         26 . The method of  claim 25 , wherein the immunogenic composition administered is a single 0.5 mL dose formulated to contain: 2 μg of each saccharide, except for 6B at 4 μg; approximately 29 μg CRM 197  carrier protein; 0.125 mg of elemental aluminum (0.5 mg aluminum phosphate) adjuvant; and sodium chloride and sodium succinate buffer as excipients.