Prediction of pneumococcal conjugate vaccine effectiveness against invasive pneumococcal disease using opsonophagocytic activity and antibody concentrations determined by enzyme-linked immunosorbent assay with 22F adsorption

Abstract

We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (≥0.2 μg/ml) and OPA assay (titer, ≥8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ≥0.2 μg/ml IgG and an OPA titer of ≥8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines.

Figures

Fig. 1.

Aggregate reverse cumulative distribution curves (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) of antipolysaccharide antibody concentrations (left) and osponophagocytic activity (right) following three doses of 7vCRM. Serum samples were obtained from studies A to D 4 weeks after a 3-dose primary series with 7vCRM (Table 1) (2, 18, 37, 46). The vertical dotted lines show the ELISA (≥0.2 μg/ml) and OPA (titer, ≥8) thresholds. The horizontal dotted lines show the effectiveness of 7vCRM against vaccine-serotype IPD (% [95% CI]) estimated in the United States (3+1 schedule) in a postlicensure study (41).

Fig. 2.

Aggregate reverse cumulative distribution curves (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) of antipolysaccharide antibody concentrations (left) and osponophagocytic activity (right) following two doses of 7vCRM. Serum samples (n = 166 for the ELISA and n = 156 for the OPA assay) were obtained from a random subset of children two months after the second primary dose in study B (46). The vertical dotted lines show the ELISA (≥0.2 μg/ml) and OPA (titer, ≥8) thresholds. The horizontal dotted lines show the effectiveness of 7vCRM against vaccine-serotype IPD (% [95% CI]) estimated in various countries (2+1 schedule) in postlicensure studies (7, 8, 31, 39).