Streptococcus pneumoniae serotype 1 burden in the African meningitis belt: exploration of functionality in specific antibodies

Abstract

Streptococcus pneumoniae serotype 1 (Sp1) constitutes an important cause of seasonal endemic meningitis in all age groups in the African meningitis belt. Despite a higher meningitis incidence, the Burkinabé population has an Sp1-specific antibody seroprevalence similar to that reported in the United Kingdom (UK). We aimed to establish whether the opsonophagocytic activity (OPA) of pneumococcal IgG naturally present in Burkina Faso differs from that seen in individuals in the UK and to compare the OPAs generated by natural and vaccine-induced immunity. Samples collected from pneumococcal vaccine-naive Burkinabé and UK subjects were matched for age (1 to 39 years) and anti-Sp1 IgG level, analyzed for OPA to 3 S. pneumoniae serotypes (1, 5, and 19A), and compared to postvaccine samples. Furthermore, the Burkinabé samples were assessed for IgG avidity and serotype-specific IgM concentrations. One hundred sixty-nine matched serum samples from both populations were selected. A greater proportion of Burkinabé subjects aged 1 to 19 years had functional Sp1 activity (OPA ≥ 8) compared to UK subjects (12% versus 2%, P < 0.001); however, the proportions were similar among adults (9%). The correlation between Sp1 IgG concentration and OPA was good (P < 0.001), but many individuals had nonfunctional IgG, which was not related to avidity. While the Sp1 IgM concentrations correlated with OPA, not all of the function in serum samples with low IgG could be attributed to IgM. Finally, vaccine-induced Sp1-specific IgG was more functional than equivalent amounts of naturally occurring IgG. In conclusion, despite a substantially higher pneumococcal meningitis incidence, no decreased functional immunity to Sp1 could be evidenced in the Burkinabé population compared to that in the population from the UK. Furthermore, the naturally induced antibodies were less functional than vaccine-induced antibodies.

FIG 1

Comparison of OPA titers against 3 S. pneumoniae serotypes between the Burkina Faso cohort and UK controls matched for age and IgG level. The dotted line indicates OPA positivity cutoff (≥8); the thin horizontal lines indicate GMC with the 95% confidence interval. Sp, serotype; B, Burkina Faso; UK, United Kingdom; N, number of subjects; ns, nonsignificant.

FIG 2

(A) Proportion of Burkinabé subjects with functional antibodies (OPA ≥ 8) by serotype (ST) and age group (y, years) after standardization for age and IgG level. (B) Proportion of Burkinabé and UK subjects with Sp1 functional antibodies (OPA ≥ 8) by age group after standardization for age and IgG level.

FIG 3

Correlation between OPA titers and IgG concentrations for Sp1 in the Burkina Faso cohort (n = 166 serum samples). Similar results were obtained for the two other serotypes. The bold horizontal line indicates the OPA positivity cutoff (≥8); the dotted lines indicate the two IgG putative protection levels (0.35 and 1 μg/ml). The blue circle indicates discrepant results with nonfunctional IgG.

FIG 4

Association between OPA values and specific IgG/IgM titers for Sp1 within the Burkina Faso cohort (univariate linear regression model, log data).

FIG 5

Comparison of Sp1-specific OPA titers between pneumococcal vaccine-naive and vaccinated populations. The dotted line indicates the OPA positivity cutoff (≥8); the solid horizontal bars indicate the GMC with the 95% confidence interval.