A RANDOMIZED COMPARISON OF 3 BIVALENT STREPTOCOCCUS-PNEUMONIAE GLYCOPROTEIN CONJUGATE VACCINES IN YOUNG-CHILDREN - EFFECT OF POLYSACCHARIDESIZE AND LINKAGE CHARACTERISTICS

Because most childhood invasive pneumococcal disease occurs before the age of 2 years, the development of a pneumococcal vaccine that is imm unogenic in infants is a priority. We assessed the safety and serum an tibody responses to two dose levels of three bivalent pneumococcal cap sular polysaccharide (CPS)-protein conjugate vaccines incorporating th e poorly immunogenic serotypes 6A and 23F. The conjugate vaccines diff ered in CPS size and chemical linkage, but all used a nontoxic cross-r eactive mutant diphtheria toxin (CRM197) as the protein carrier. 118 y oung children 18 to 30 months of age received a single immunization wi th one of the three glycoconjugates or with licensed pneumococcal vacc ine. Sera were obtained before and 1 month after immunization and anal yzed by enzyme-linked immunosorbent assay for serotype-specific antibo dy titers. The 23F CPS was more immunogenic than the 6A CPS in all vac cine 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 associa ted with an increase in immunogenicity, and the characteristics of the CPS and of the CPS-protein linkage appear to influence the antibody r esponse.