Functional antibodies elicited by two heptavalent pneumococcal conjugate vaccines in the Finnish Otitis Media Vaccine Trial

Abstract

In the Finnish Otitis Media Vaccine Trial, the now-licensed pneumococcal conjugate vaccine containing polysaccharides conjugated to protein CRM(197) (PncCRM) and the experimental pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine (PncOMPC), showed similar efficacy profiles against acute otitis media despite different antibody concentrations in sera. We now report the opsonophagocytic activities (OPA) in these sera. OPA, antibody concentration, and avidity for serotypes 6B, 19F, and 23F were determined in sera of infants who received either pneumococcal conjugate (PCV) or control vaccine at 2, 4, and 6 months of age and either the homologous or pneumococcal polysaccharide vaccine at 12 months of age. OPA varied by vaccine and serotype. The majority of PCV recipients had positive OPA after the fourth dose, while OPA was undetectable in the control group. Coinciding with the efficacy data, the concentration of antibodies required for 50% killing was low for 6B and high for 19F for both PCVs. Contradictory to the efficacy data, PncOMPC induced lower functional capacity to 23F than PncCRM. OPA correlated with antibody concentration, while avidity and functional capacity of antibodies showed no correlation. The OPA data provide valuable additional information for serotype-specific differences in protection and when evaluating serotype-specific immunogenicity and should thus be considered when defining serological correlates of protection.

FIG. 1.

The correlation (Spearman's correlation coefficient; P < 0.001 for all serotypes and time points) and a linear regression model for the IgG anti-6B, -19F, and -23F antibody concentrations (EIA, μg/ml) and OPA titers after three (7 months) and four (13 months) doses of vaccine. The children were immunized with 7-valent pneumococcal conjugate vaccine (PncCRM or PncOMPC) at 2, 4, and 6 months of age and either with the homologous vaccine or 23-valent polysaccharide vaccine (PncPS) at 12 months of age. All children boosted with PncPS had previously received three doses of PncOMPC.