In Fig 1A, in vitro type-1 (IFN-γ) and type-2 (IL-5 and IL-13) T

In Fig. 1A, in vitro type-1 (IFN-γ) and type-2 (IL-5 and IL-13) T-cell memory cytokine responses to the vaccine

carrier protein CRM197 are shown for 132 study children with data available at both 3 and 9 months of age: type-1 and type-2 CRM197 responses were found to be higher in PCV-vaccinated children compared to unvaccinated children at both 3 and 9 months of age, which confirms that both 7vPCV immunisation schedules induced persistent T-cell memory responses. The higher Th2-recall response at 3 months of age in the Selleck Pfizer Licensed Compound Library neonatal compared to the infant group (IL-5, p = 0.044; IL-13, p = 0.051) [18], was no longer apparent at 9 months Crenolanib manufacturer of age. There was no evidence that co-immunisation with BCG at birth influenced CRM197-induced T-cell responses at 3 months [18] or 9 months of age (data not presented). Accordingly, at both 3 and 9 months of age serum pneumococcal serotype-specific IgG antibody titres were found to be higher and exceed the assumed clinically protective level of 0.35 μg/ml for most PCV serotypes in children

who had received 7vPCV compared to those who had not, confirming the induction of protective immune responses in both immunisation schedules (Fig. 1B). We next performed a comprehensive immuno-phenotypic analysis of the CRM197-specific T-cell memory response at 9 months to confirm that recall responses were similar under neonatal and infant immunisation schedules. Comparison of in vitro T-cell memory cytokine responses to the vaccine carrier protein CRM197 demonstrated that recall responses were characterized by a mixed pattern of type-1/type-2 responses and were comparable in the neonatal and infant groups ( Fig. 2A), with only a minority of children displaying exclusively

Th2 responses ( Fig. 2B). We next progressed to genome-wide expression profiling of T-cell memory responses in a subpopulation of randomly selected children (n = 25 per group). In the neonatal group in vitro mafosfamide CRM197 stimulation was found to result in a significant differential expression of 105 genes and in the infant group of 140 genes (78 mutual) ( Supplementary Fig. 1A and Table 1). The expression levels of these CRM197 response genes did not differ between the two vaccination groups ( Supplementary Fig. 1B) and this is illustrated in Fig. 2C for genes that are involved in T-helper cell differentiation or responsiveness. Since microarray data were based on pooled RNA samples and could be influenced by individual outliers, we performed quantitative RT-PCR analysis for a defined set of memory T-cell related genes in individual samples. In line with the microarray data, mRNA expression levels were similar in the two vaccination groups ( Fig. 2D).

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