Abstract

BackgroundA 9-valent pneumococcal conjugate vaccine (PCV-9), given in a 3-dose schedule, protected Gambian children against pneumococcal disease and reduced nasopharyngeal carriage of pneumococci of vaccine serotypes. We have studied the effect of a booster or delayed primary dose of 7-valent conjugate vaccine (PCV-7) on antibody and nasopharyngeal carriage of pneumococci 3–4 years after primary vaccination.Methodology/Principal FindingsWe recruited a subsample of children who had received 3 doses of either PCV-9 or placebo (controls) into this follow-up study. Pre- and post- PCV-7 pneumococcal antibody concentrations to the 9 serotypes in PCV-9 and nasopharyngeal carriage of pneumococci were determined before and at intervals up to 18 months post-PCV-7. We enrolled 282 children at a median age of 45 months (range, 38–52 months); 138 had received 3 doses of PCV-9 in infancy and 144 were controls. Before receiving PCV-7, a high proportion of children had antibody concentrations >0.35 µg/mL to most of the serotypes in PCV-9 (average of 75% in the PCV-9 and 66% in the control group respectively). The geometric mean antibody concentrations in the vaccinated group were significantly higher compared to controls for serotypes 6B, 14, and 23F. Antibody concentrations were significantly increased to serotypes in the PCV-7 vaccine both 6–8 weeks and 16–18 months after PCV-7. Antibodies to serotypes 6B, 9V and 23F were higher in the PCV-9 group than in the control group 6–8 weeks after PCV-7, but only the 6B difference was sustained at 16–18 months. There was no significant difference in nasopharyngeal carriage between the two groups.Conclusions/SignificancePneumococcal antibody concentrations in Gambian children were high 34–48 months after a 3-dose primary infant vaccination series of PCV-9 for serotypes other than serotypes 1 and 18C, and were significantly higher than in control children for 3 of the 9 serotypes. Antibody concentrations increased after PCV-7 and remained raised for at least 18 months.

Highlights

  • Streptococcus pneumoniae is estimated to cause nearly one million childhood deaths each year [1]

  • There is a high burden of pneumococcal disease in The Gambia [4,5] where the pneumococcus is the most prevalent bacterial pathogen isolated from children with pneumonia and is responsible for about 50% of cases of pyogenic meningitis [3,4,6]

  • The 9-valent pneumococcal conjugate vaccine (PCV-9) given in a 3-dose schedule beginning at 6 weeks of age, with a minimum of 4-week intervals between doses, induced protective levels of anti-pneumococcal antibodies [11] and provided protection against invasive pneumococcal diseases (IPD), pneumonia and all-cause mortality in Gambian children up to the end of follow-up at age 30 months [12]

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Summary

Introduction

Streptococcus pneumoniae (the pneumococcus) is estimated to cause nearly one million childhood deaths each year [1]. The 9-valent pneumococcal conjugate vaccine (PCV-9) given in a 3-dose schedule beginning at 6 weeks of age, with a minimum of 4-week intervals between doses, induced protective levels of anti-pneumococcal antibodies [11] and provided protection against IPD, pneumonia and all-cause mortality in Gambian children up to the end of follow-up at age 30 months [12]. Gambian children who received primary vaccination with 2 or 3 doses of a 5-valent PCV in infancy showed immunologic memory at 24 months of age [14], but there are few data on declines in antibody concentration or on the persistence of immunologic memory beyond this period in children in developing countries. A 9-valent pneumococcal conjugate vaccine (PCV-9), given in a 3-dose schedule, protected Gambian children against pneumococcal disease and reduced nasopharyngeal carriage of pneumococci of vaccine serotypes. We have studied the effect of a booster or delayed primary dose of 7-valent conjugate vaccine (PCV-7) on antibody and nasopharyngeal carriage of pneumococci 3–4 years after primary vaccination

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