Enhancing immunogenicity of streptococcus pneumoniae polysaccharide-protein conjugates

Abstract

The present invention provides immunogenic compositions having one or more polysaccharide-protein conjugates in which one or more polysaccharides from Streptococcus pneumoniae bacterial capsules are conjugated to a carrier protein in an aprotic solvent such as dimethylsulfoxide (DMSO). The present invention also provides methods for providing an enhanced immune response to a pneumococcal polysaccharide protein conjugate vaccine comprising administering to a human subject an immunogenic composition comprising polysaccharide-protein conjugates prepared in DMSO conditions.

1 - 44 . (canceled) 
     
     
         45 . A method of preparing a pneumococcal polysaccharide-protein conjugate by reductive amination, the method comprising:
 a) reacting a  Streptococcus pneumoniae  polysaccharide selected from serotypes 3, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F with an amount of an oxidant to form an activated polysaccharide having an activation level from 0.05 to 0.22; and   b) reacting the activated polysaccharide with a carrier protein in an aprotic solvent to form a polysaccharide-protein conjugate;   
       wherein the resulting polysachharide-protein conjugate has a lysine loss value between 7.0 and 18.0 inclusive. 
     
     
         46 . The method of  claim 45 , wherein the activation level is from 0.09 to 0.22. 
     
     
         47 . The method of  claim 45 , wherein the reacting in step b) is in the presence of a reducing agent. 
     
     
         48 . The method of  claim 45 , wherein the carrier protein is selected from the group consisting of tetanus toxoid, diphtheria toxoid, and CRM 197 . 
     
     
         49 . The method of  claim 48 , wherein the carrier protein is CRM 197 . 
     
     
         50 - 53 . (canceled)