Immune response in infants to the heptavalent pneumococcal conjugate vaccine against vaccine-related serotypes 6A and 19A

Abstract

The currently available 7-valent pneumococcal conjugate vaccine (PCV7) elicits good immune response to and is effective against vaccine serotypes. However, its effectiveness against vaccine-related serotypes is variable. Serum samples were obtained 1 month after the last vaccination from 31 infants immunized with PCV7 at 2, 4, and 6 months of age. The sera were used to determine immunoglobulin G antibody levels to eight serotypes (seven vaccine serotypes and serotype 19A) with enzyme-linked immunosorbent assay (ELISA) and opsonic capacity against 11 serotypes (seven vaccine serotypes, serotypes 19A and 6A, and nonvaccine serotypes 5 and 7F) using a multiplexed opsonization assay. ELISA results showed antibody concentrations varied between 1.84 and 10.49 microg/ml, and all subjects had antibody concentrations of >or=0.35 microg/ml for all serotypes, including serotype 19A. In contrast, the opsonic index was detectable (i.e., opsonic index >or= 8) in all children for the seven vaccine serotypes, 81% for serotype 6A, and merely 19% for serotype 19A. PCV7 shows good immunogenicity for vaccine serotypes in infants after a primary series. PCV7 does not elicit opsonic antibodies to serotype 19A. ELISA may thus be an inadequate surrogate assay for evaluating the response for cross-reactive serotypes in infants.

FIG. 1.

Reverse cumulative distribution curves for vaccine type serotypes generated by PCV7 in infants. (A) Antibody concentration (μg/ml); (B) opsonic index.

FIG. 2.

Opsonic index (y axis) versus antibody concentration (x axis) for vaccine-type serotypes (4, 6B, 9V, 14, 18C, and 23F) and VRT 19A. The vertical and horizontal dotted lines represent the antibody titer of 0.35 μg/ml and opsonic detection limit of 8 for the OPA, respectively.

FIG. 3.

Cross-opsonic capacities for serogroup 19 (A) and serogroup 6 (B). The opsonic index for the VRTs (y axis) versus opsonic index for VTs (x axis) is shown.

FIG. 4.

Reverse cumulative distribution curves of opsonic indices generated by PCV7. (A) Serotypes 19F and 19A; (B) serotypes 6B and 6A. The vertical dotted line represents the opsonic detection limit of 8 for the OPA.