Oral polio vaccination failure in urban slum children is associated with malnutrition and evidence of chronic inflammation

Abstract Oral vaccines for polio (OPV) and rotavirus have been shown to be much less effective in poor children in the developing world. The reason(s) for oral vaccine failure in this setting has been unknown. We hypothesized that failure of orally administered vaccines such as OPV was due to tropical enteropathy and resultant inflammation from endotoxin exposure. We tested this hypothesis in a cohort of children followed from birth in an urban slum of Dhaka Bangladesh. Response to oral poliovirus vaccine was measured in the children who received the recommended minimum of three doses of OPV by age 6 months. Diminished antibody responses to OPV were associated with malnutrition, serum endotoxin-specific antibodies, and shorter breastfeeding duration. In a subset of these children, we investigated the mechanism for vaccine failure using a systems-immunology approach, performing comprehensive cellular assays on peripheral blood mononuclear cells, including a single-cell mass-spectrometry based assessment of cellular phenotypes and functional capacities. From this analysis, children with vaccine failure exhibited globally reduced cellular responsiveness to a range of cytokine stimulations, as well as elevated pro-inflammatory cytokine expression. These data indicate that oral vaccine failure in this at-risk group is related to malnutrition, gut barrier dysfunction and shorter duration of breast-feeding in early childhood, and is associated with a chronic inflammatory immune phenotype.