Abstract
BackgroundBCG immunogenicity in infants differs between populations and these differences have been attributed to various factors. In this study, the influence of geographical location, season of birth, timing of vaccination, micronutrient status (zinc) and inflammatory status (C-reactive protein, CRP) were assessed.MethodsImmunogenicity was assessed by cytokine signature in culture supernatants from diluted whole blood samples stimulated with M. tuberculosis PPD, using a multiplex bead assay. Results were correlated with the plasma zinc and CRP concentrations at the time of sampling, and with interview and household data. BCG vaccinated infants were recruited in Malawi, The Gambia and the UK.ResultsIn Malawi, infants vaccinated within the first week after birth showed lower production of most cytokines measured than those vaccinated later. The number of cytokines showing significant differences between Malawian and Gambian infants decreased after adjusting for season of birth. In Malawi, a proportion of infants had zinc deficiency and elevated plasma CRP (>10 mg/L), but neither zinc deficiency nor high CRP was associated with production of any of the cytokines measured.ConclusionsThe cytokine/chemokine signatures observed in response to M. tuberculosis PPD in infants at 3 months post BCG vaccination were affected by geographical location, season of birth, and timing of vaccination but not associated with the concentration of plasma zinc or inflammatory status. These factors should be considered in future trials of new TB vaccines.
Highlights
BCG immunogenicity in infants differs between populations and these differences have been attributed to various factors
The Gambian infants vaccinated at birth showed more than twice the median concentration of IFN-γ, IL-1α, IL-1ra, IL-6, TNF-β, TGF-α, IL-12p70 and RANTES in response to M. tb purified protein derivative (PPD) compared to Malawian infants vaccinated at birth (P < 0.05) (Figure 1)
The net MCP-1 responses to M. tb PPD and PHA were very low in Gambian infants, but this was due to high background levels (Table 2)
Summary
BCG immunogenicity in infants differs between populations and these differences have been attributed to various factors. Despite successful global TB control efforts and decreasing TB incidence [1], the variable efficacy and immunogenicity of the BCG vaccine in different populations [2,3,4] highlights the ongoing need to develop new vaccines or delivery strategies. Better understanding of the factors leading to variations in immune responses to BCG and how different immune responses correlate with the efficacy of BCG, may help to evaluate the efficacy of new TB vaccines. Zinc deficiency causes an imbalance in immune function by shifting a Th1 to a Th2 response, which results in cell-mediated immune dysfunction that may increase susceptibility to various pathogens [6]
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