Avidity and subclasses of IgG after immunization of infants with an 11-valent pneumococcal conjugate vaccine with or without aluminum adjuvant.

Finnish and Israeli infants received an 11-valent mixed-carrier pneumococcal conjugate vaccine with or without aluminum adjuvant at 2, 4, 6, and 12 months of age. The relative avidity of serotype 1-, 5-, 6B-, 14-, 19F-, and 23F-specific IgG antibodies in serum obtained at 7, 12, and 13 months of age was measured by EIA, using thiocyanate as a chaotropic agent. For all serotypes, except 14, avidity increased between the ages of 7 and 12 months. After boosting at 12 months, avidity further increased for all serotypes. The adjuvant improved antibody avidity against serotype 5. The IgG antibodies produced were mainly IgG1 subclass, although some infants also produced IgG2 after boosting. In conclusion, the immunization of infants with this 11-valent pneumococcal conjugate vaccine increased avidity of IgG, suggesting successful immunologic priming.

Cross-reactivity of antibodies to type 6B and 6A polysaccharides of Streptococcus pneumoniae, evoked by pneumococcal conjugate vaccines, in infants.

Streptococcus pneumoniae serotypes 6B and 6A are important causes of infections, yet only 6B is included in current vaccines. It is, therefore, crucial to evaluate whether functional antibodies are produced against both types after vaccination. Concentration and opsonophagocytic activity (OPA) of antibodies to 6B and 6A polysaccharides were determined in serum samples from infants immunized with 3 different pneumococcal conjugate vaccines containing serotype 6B. In all vaccine groups, a significant correlation was found between the anti-6B and -6A antibody concentration and OPA. However, OPA to the vaccine serotype was detectable more commonly than OPA to the cross-reactive type. Furthermore, 5%-15% of the serum samples showed high OPA against the 6B but not the 6A strain. On average, 2-6 times more anti-6B antibodies were needed for 50% opsonophagocytic killing of the type 6A than the type 6B strain. Although pneumococcal type 6B conjugate vaccines elicit antibodies that cross-react with type 6A, not all anti-6B antibodies are functionally cross-reactive.

Opsonophagocytic activity against Streptococcus pneumoniae type 19F in allogeneic BMT recipients before and after vaccination with pneumococcal polysaccharide vaccine.

Opsonophagocytic activity (OPA) of pneumococcal polysaccharide (Pnc PS) antibodies in vitro, a measure of antibody functional activity, usually correlates with specific IgG antibody concentrations measured by an EIA method. In order to investigate the functional activity of specific Pnc PS antibodies, we determined IgG antibodies to Pnc PS type 19F by an EIA method and OPA against Pnc type 19F by a killing assay in a randomized study, where 23 adult allogeneic BMT recipients were vaccinated with Pnc PS vaccine at 8 months (early group) and 21 recipients at 20 months (late group) after transplantation. Serum samples drawn before BMT, before vaccination, and at 1 and 16 months after vaccination were available from 27, 35, 34 and 30 patients, respectively. The geometric mean anti-Pnc 19F concentrations were 4.3, 1.3, 1.6 and 1.3 microg/ml in the early group and 3.8, 0.9, 0.6 and 0.6 microg/ml in the late group before transplantation, before vaccination, and at 1 and 16 months after vaccination, respectively. OPA (titre > or = 8) was found in 10/27, 5/35, 5/34 and 6/30 patients before BMT, before vaccination, and at 1 and 16 months after vaccination, respectively. The specific IgG antibody concentration and OPA correlated with each other before BMT, and in the early group patients before and at 1 month after vaccination. The results demonstrate that after Pnc PS vaccination allogeneic BMT recipients have antibodies with low functional activity to a Pnc PS antigen associated with low specific IgG responses. There is a need to study new Pnc conjugate vaccines in multi-dose schedules for their capacity to elicit higher specific antibody concentrations with high OPA in BMT recipients.

Are the opsonophagocytic activities of antibodies in infant sera measured by different pneumococcal phagocytosis assays comparable?

Host protection against Streptococcus pneumoniae is mainly mediated by opsonin-dependent phagocytosis. Several techniques for measuring opsonophagocytic activity (OPA) of antibodies to S. pneumoniae have been standardized and used. These include the viable cell-assay, flow-cytometric assays, and an assay utilizing radiolabeled bacteria. Using these different methods, we measured the OPA of antibodies to S. pneumoniae types 6B and 19F from the sera of infants immunized with a pneumococcal conjugate vaccine, PncCRM. Generally, the results obtained by the various techniques correlated well, although serotype-specific differences were found (6B, r = 0.78 to 0.95, P < 0.001; 19F, r = 0.50 to 0.84, P < 0.001). The same serotype-specific differences were observed for the relationship between the concentrations of specific immunoglobulin G antibodies measured by enzyme immunoassay and the OPA. Since the sensitivities of the OPA assays differed, the most prominent discrepancies between the techniques were found at low antibody concentrations.