IMMUNOLOGICAL PRIMING OF YOUNG-CHILDREN BY PNEUMOCOCCAL GLYCOPROTEIN CONJUGATE, BUT NOT POLYSACCHARIDE, VACCINES

Background. Streptococcus pneumoniae is the most common cause of invas ive bacterial disease and otitis media in infants and young children. Licensed pneumococcal polysaccharide vaccines are not reliably immunog enic in children younger than 2 years of age; therefore pneumococcal g lycoprotein conjugate vaccines are currently being evaluated for safet y, immunogenicity and efficacy in various age groups. Methods, During a 12-month period we determined the kinetics of pneumococcal IgG antib ody in 60 children who received primary immunization with one dose of bivalent (serotypes 6A and 23F) pneumococcal polysaccharide-CRM(197) v accines at 18 to 30 months of age, To assess immunologic priming a sub group of 20 subjects received secondary immunization with pneumococcal polysaccharide vaccine, including serotypes 6B and 23F, at 11 to 20 m onths after primary immunization, Pneumococcal-specific IgG subclass d istributions were also evaluated in the subgroup. Results. In the 12 m onths after primary immunization with glycoprotein conjugate vaccine, geometric mean pneumococcal IgG antibody concentrations to 6B and 23F serotypes remained stable. Pneumococcal polysaccharide vaccine induced a greater anamnestic response in children primed with the glycoprotei n conjugate vaccines (13- to 40-fold increases to geometric mean conce ntrations of 6 to 30 mu g/ml for type 23F), than in those primed with polysaccharide (2- to 4-fold increases). A greater IgG response to pne umococcal serotype 23F than to 6B was observed with both primary and s econdary immunization. The serotype-specific pneumococcal IgG antibody response was virtually restricted to the IgG1 subclass after primary immunization, but secondary immunization elicited antibodies of IgG1 a nd IgG2 subclasses. Conclusions. These glycoprotein conjugate vaccines appear to prime for anamnestic IgG antibody responses to subsequent i mmunization with polysaccharide vaccine, suggesting that the polysacch aride-CRM(197) vaccine effectively induces a predominantly T cell-depe ndent immune response, The greater IgG response to 23F than to 6B indi cates that pneumococcal serotype is a major determinant of immunogenic ity of pneumococcal glycoprotein conjugate vaccines.