Multivalent pneumococcal polysaccharide-protein conjugate composition
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. Methods for making an immunogenic conjugate comprising Streptococcus pneumoniae serotype 19A polysaccharide are also provided in which the serotype 19A polysaccharide is co-lyophilized with a carrier protein and conjugation is carried out in dimethyl sulfoxide (DMSO) via a reductive amination mechanism.
1. A multivalent immunogenic pneumococcal conjugate composition comprising
polysaccharide-protein conjugates comprising individual Streptococcus pneumoniae capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F covalently linked to CRM 197 , wherein said serotype 19A polysaccharide is co-lyophilized with said CRM 197 , wherein said composition comprises less than about 25% free serotype 19A polysaccharide compared to the total amount of serotype 19A polysaccharide, and wherein between 60% and 74% of said conjugates comprising serotype 19A have a Kd below or equal to 0.3 in a CL-4B column;
an aluminum phosphate adjuvant; and
a physiologically acceptable vehicle.