A randomized comparison of three bivalent Streptococcus pneumoniae glycoprotein conjugate vaccines in young children: effect of polysaccharide size and linkage characteristics

Abstract

Because most childhood invasive pneumococcal disease occurs before the age of 2 years, the development of a pneumococcal vaccine that is immunogenic in infants is a priority. We assessed the safety and serum antibody responses to two dose levels of three bivalent pneumococcal capsular polysaccharide (CPS)-protein conjugate vaccines incorporating the poorly immunogenic serotypes 6A and 23F. The conjugate vaccines differed in CPS size and chemical linkage, but all used a nontoxic cross-reactive mutant diphtheria toxin (CRM197) as the protein carrier. 118 young children 18 to 30 months of age received a single immunization with one of the three glycoconjugates or with licensed pneumococcal vaccine. Sera were obtained before and 1 month after immunization and analyzed by enzyme-linked immunosorbent assay for serotype-specific antibody titers. The 23F CPS was more immunogenic than the 6A CPS in all vaccine formats. The most immunogenic 23F conjugate vaccine consisted of native CPS directly linked to the carrier protein; smaller CPS or the use of a six-carbon linker did not appear to enhance immunogenicity in these young children. Conjugation of two pneumococcal CPSs is associated with an increase in immunogenicity, and the characteristics of the CPS and of the CPS-protein linkage appear to influence the antibody response.