Long-term impact of pneumococcal polysaccharide vaccination on nasopharyngeal carriage in children previously vaccinated with various pneumococcal conjugate vaccine regimes

Abstract

Previously, the Fiji Pneumococcal Project (FiPP) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (PCV7 and 23vPPV, respectively). Immune hyporesponsiveness was observed in children vaccinated with 23vPPV at 12 months of age compared with children who did not receive 23vPPV. Here we assess the long-term impact of 23vPPV vaccination on nasopharyngeal carriage rates and densities of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Nasopharyngeal swabs (n=194) were obtained from healthy children who participated in FiPP (now aged 5–7 years). S. pneumoniae were isolated and identified by standard culture-based methods, and serotyped using latex agglutination and the Quellung reaction. Carriage rates and densities of S. pneumoniae, H. influenzae, S. aureus and M. catarrhalis were determined using real-time quantitative PCR. There were no differences in the rate or density of S. pneumoniae, H. influenzae or M. catarrhalis carriage by PCV7 dose or 23vPPV vaccination in the vaccinated participants overall. However, differences were observed between the two main ethnic groups: Fijian children of Indian descent (Indo-Fijian) were less likely to carry S. pneumoniae, H. influenzae and M. catarrhalis, and there was evidence of a higher carriage rate of S. aureus compared with indigenous Fijian (iTaukei) children. Polysaccharide vaccination appeared to have effects that varied between ethnic groups, with 23vPPV vaccination associated with a higher carriage rate of S. aureus in iTaukei children, while there was a lower carriage rate of S. pneumoniae associated with 23vPPV vaccination in Indo-Fijian children. Overall, polysaccharide vaccination had no long-term impact on pneumococcal carriage, but may have impacted on S. aureus carriage and have varying effects in ethnic groups, suggesting current WHO vaccine schedule recommendations against the use of 23vPPV in children under two years of age are appropriate.

The association between pneumococcal vaccination, ethnicity, and the nasopharyngeal microbiota of children in Fiji

“…Our previous studies in Fiji [25, 30] found significant differences in bacterial carriage between iTaukei and FID children but only examined a limited number of bacterial species. Here, we found substantial differences in the entire nasopharyngeal microbiota based on ethnicity.…”

“…There is evidence that social contact can influence microbiota [41] but the relative importance of social contact compared with other factors as a determinant of microbiota is unknown. In Fiji, the two main ethnic groups have similar household income [30] so it is unlikely that socio-economic status, a known risk factor for pneumococcal carriage [23], contributes to the observed differences in nasopharyngeal bacteria between iTaukei and FID children. Given the complexity and interconnected nature of factors that can determine microbiota, it is likely multiple factors are involved in the underlying differences in microbial composition between ethnic groups in Fiji.…”

“…Previously, we conducted the Fiji Pneumococcal Project (FiPP), a randomised phase II vaccine trial that evaluated various schedules of PCV7 followed by the 23-valent pneumococcal polysaccharide vaccine as a booster at 12 months of age [26–29]. Results from FiPP at 17 months of age, and a long-term follow-up to the study, highlighted differences in carriage prevalence of S. pneumoniae , S. aureus , H. influenzae and M. catarrhalis between the two main ethnic groups [25, 30], suggesting they have distinct microbial profiles. We also found that the 23-valent pneumococcal polysaccharide vaccine given at 12 months of age had differential effects on long-term carriage of S. pneumoniae and S .…”

“…We also found that the 23-valent pneumococcal polysaccharide vaccine given at 12 months of age had differential effects on long-term carriage of S. pneumoniae and S . aureus for the two ethnic groups [30].…”

Prevnar-13 vaccine failure in a mouse model for vitamin A deficiency

“…These conjugates induce robust, T-dependent antibody responses in young children. Routine immunizations with the pneumococcal conjugate vaccine have resulted in highly significant reductions in pneumococcus bacteremia among young children [4, 5]. …”