Molecular epidemiology of pneumococci obtained from Gambian children aged 2–29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine

BACKGROUND: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children METHODS: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2-29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST. RESULTS: Twenty-nine different serotypes were identified; serotypes 14, 19A, 12F, 5, 23F, and 1 were common and accounted for 58.3% of all serotypes overall. MLST analysis showed 72 sequence types (STs) of which 46 are novel. eBURST analysis using the stringent 6/7 identical loci definition, grouped the isolates into 17 clonal complexes and 32 singletons. The population structure of the 8 serotype 1 isolates obtained from 4 vaccinated and 2 unvaccinated children were the same (ST 618) except that one (ST3336) of the isolates from an unvaccinated child had a novel ST which is a single locus variant of ST 618. CONCLUSION: We provide the first background data on the genetic structure of S. pneumoniae causing IPD prior to PC7V use in The Gambia. This data will be important for assessing the impact of PC7V in post-vaccine surveillance from The Gambia

Pneumococcal Antibody Concentrations and Carriage of Pneumococci more than 3 Years after Infant Immunization with a Pneumococcal Conjugate Vaccine

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: We 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/SIGNIFICANCE: Pneumococcal 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

Dissociation between tuberculin skin test and in vitro IFN-gamma responses following neonatal BCG vaccination

The in vitro IFN-gamma response to tuberculin was recently proposed as a correlate of vaccine-induced immunity to tuberculosis. IFN-gamma also plays a central role in the tuberculin skin test (TST), commonly used as a marker of mycobacterial infection. However, the use of TST as a marker of immunity to tuberculosis is limited for reasons ascribed mainly to interference by environmental mycobacteria. We prospectively investigated the relationship between the TST and cytokine responses to BCG in early infancy, a cohort with relatively low exposure to environmental mycobacteria. Neonatal BCG vaccination induced positive TST responses and predominant IFN-gamma responses to tuberculin in most newborns. However, the production of IFN-gamma, IL-5 and IL-13 was similar in TST responders and non-responders, and there was no significant correlation between the size of TST response and cytokine production. These results indicate that the IFN-gamma assay provides different information than TST in BCG-vaccinated newborns and could be a better marker of vaccine-induced immunity

Nasopharyngeal carriage of <i>Streptococcus pneumoniae</i> before and after vaccination with a single dose of PCV-7.

<p>NA = Not applicable.</p><p>*Number of children.</p><p>**Number of serotypes (some children had multiple serotypes on a single visit: they have been included in all those serotype groups).</p>†<p>P value = 0.057 before Holm's correction for multiple significance tests.</p>‡<p>P value = 0.037 before Holm's correction for multiple significance tests.</p

A consort diagram indicating number of study participants per study group and visit.

<p>A consort diagram indicating number of study participants per study group and visit.</p

Proportions of children aged 3–4 years with antibody concentration ≥0.35 µg/mL before and after vaccination with PCV-7.

<p>*P value = 0.0009 before Holm's correction for multiple significance tests.</p><p>**P value = 0.0001 before Holm's correction for multiple significance tests.</p>†<p>P value = 0.037 before Holm's correction for multiple significance tests.</p>‡<p>P value = 0.043 before Holm's correction for multiple significance tests.</p

Geometric means (95% CI) of IgG antibody concentrations (µg/mL) before and after boosting with PCV-7 in the group that previously had placebo (Control) or PCV-9 (Vaccinated).

<p>*The GMs of antibodies to these serotypes were significantly higher in the vaccinated group than the controls.</p

Geometric mean of IgG antibody concentrations (µg/mL) before and after vaccination with PCV-7 in the two groups (visit 1 = pre-vaccination).

<p>Geometric mean of IgG antibody concentrations (µg/mL) before and after vaccination with PCV-7 in the two groups (visit 1 = pre-vaccination).</p