Outpacing the pneumococcus: Antibody dynamics in the first few days following pneumococcal capsular antigen stimulation

Abstract

Children in developing countries are frequently exposed to the pneumococcus, but few develop invasive pneumococcal disease (IPD). We test the hypothesis that natural variation exists in the rapidity of IgG responses following exposure to pneumococcal polysaccharides, and that these differences are sufficiently great to affect susceptibility to and outcome of IPD. We recruited children aged 24-36 months, who had recovered from IPD, and age-matched healthy controls and vaccinated them with 1 dose of the 23-valent PPV to mimic natural exposure. We collected serum samples after vaccination and analysed the dynamics of anti-polysaccharide antibody responses to several capsular antigens. Mean IgG response times to different serotypes were 6.4-7.3 days, with standard deviations of 0.9-1.85 days, suggesting a natural range in response times of up to 7 days. Serotype 1 elicited the largest fold-rise, serotype 23F the smallest. The proportion of responses achieved by day 7 was similar in children with a history of IPD and healthy children. There was considerable natural variation in the rapidity of anti-capsular IgG responses extending over 4-7 days. There was no evidence to suggest that children who have experienced IPD respond more slowly to heterologous pneumococcal capsular antigens than do healthy children.

Figure 1

Geometric mean concentrations of antibodies to pneumococcal serotypes 1, 6B, 14, 19F and 23F, before and after immunization with polysaccharide vaccine in healthy children (n = 36).

Figure 2

Cumulative distribution curves representing the proportion of children reaching the response threshold (half of the maximum) against time since vaccination for serotype 1, 6B, 14, 19F and 23F.

Figure 3

Proportion of the total antibody concentration rise achieved by 7 days for five capsular antibodies among Prior IPD and Healthy Control groups. Box plots show 25^th and 75^th percentiles, error bars show 10^th and 90^th percentailes and median values are shown as (−). Proportional rise = C₇ − C₀/C₁₁ − C₀ where C₀, C₇ and C₁₁ represent concentrations on day 0, 7 and 11 respectively. IPD = Invasive Pneumococcal Disease *P < 0.05 (Wilcoxon rank sum test).