Kinetics and avidity of antibodies evoked by heptavalent pneumococcal conjugate vaccines PncCRM and PncOMPC in the Finnish Otitis Media Vaccine Trial

Abstract

The licensure of new pneumococcal conjugate vaccines (PCVs) relies on immunogenicity data. When defining correlates of protection, vaccine efficacy data must be included. In the FinOM Vaccine Efficacy Trial, the PncOMPC vaccine showed an efficacy profile similar to that of the licensed PncCRM vaccine despite different antibody responses after primary and booster vaccinations. We determined antibody kinetics and avidities in a subgroup of infants participating in the FinOM trial. A total of 166 infants in three vaccine groups were immunized at 2, 4, 6, and 12 months of age with 7-valent PCV, PncCRM or PncOMPC, or hepatitis B vaccine. Concentrations of serum immunoglobulin G (IgG) against pneumococcal capsular polysaccharides were determined at 2, 4, 6, 7, 12, 13, and 24 months of age, and the avidity index (AI) to serotypes 6B, 19F, and 23F were determined at 7, 12, 13, and 24 months of age by enzyme immunoassay. Both PCVs were highly immunogenic, but they demonstrated different kinetics of antibody response; the concentration of IgG against serotypes 6B, 19F, and 23F declined faster after the third and fourth doses of vaccine in the PncCRM group than in the PncOMPC group. For both PCVs, the mean AI of anti-6B and -23F, but not of anti-19F, increased during the follow-up, which is in line with serotype-specific protection in the FinOM trial. Our data suggest that the kinetics and avidities of antibodies should be considered, in addition to antibody responses, when defining correlates of protection.

FIG. 1.

GMC against each of the serotypes of a 7-valent pneumococcal conjugate vaccine at different time points in infants immunized at 2, 4, 6, and 12 months of age with PncCRM (n = 54 to 56), PncOMPC (n = 44 to 55), or a control vaccine (n = 53 or 54).

FIG. 2.

Reverse cumulative distribution curves demonstrating the percentages of children achieving various serum IgG antibody concentrations against each of the vaccine serotypes at various ages. The children were immunized at 2, 4, 6, and 12 months of age with a pneumococcal conjugate vaccine, PncCRM (n = 54 to 56) or PncOMPC (n = 44 to 55).

FIG. 3.

Percentages and 95% confidence intervals of infants with an antibody concentrations of ≥0.35 μg/ml at 7, 12, 13, and 24 months of age. The infants were immunized at 2, 4, 6, and 12 months of age with a 7-valent pneumococcal conjugate vaccine, PncCRM (n = 54 to 56) or PncOMPC (n = 44 to 55), or a control vaccine (n = 53 or 54).

FIG. 4.

MAIs and 95% confidence intervals of anti-pneumococcal type 6B, 19F, and 23F capsular polysaccharide IgG antibodies in infants immunized at 2, 4, 6, and 12 months of age with 7-valent pneumococcal conjugate vaccine, PncCRM (n = 53 to 56) or PncOMPC (n = 44 to 53), or a control vaccine (n = 40 to 47).