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

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

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

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

Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage

Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection