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Early aberrant antibody responses of aeroallergen sensitised people to subclinical bacterial infectionEarly aberrant antibody responses, aeroallergen sensitised people, subclinical bacterial infection
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Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways.
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OPTIMUM study protocol: an adaptive randomised controlled trial of a mixed whole-cell/acellular pertussis vaccine scheduleCombination vaccines containing whole-cell pertussis antigens were phased out from the Australian national immunisation programme between 1997 and 1999 and replaced by the less reactogenic acellular pertussis (aP) antigens. In a large case-control study of Australian children born during the transition period, those with allergist diagnosed IgE-mediated food allergy were less likely to have received whole-cell vaccine in early infancy than matched population controls (OR: 0.77 (95% CI, 0.62 to 0.95)). We hypothesise that a single dose of whole-cell vaccine in early infancy is protective against IgE-mediated food allergy.
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Transplacental Innate Immune Training via Maternal Microbial Exposure: Role of XBP1-ERN1 Axis in Dendritic Cell Precursor ProgrammingWe recently reported that offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance to allergic airways inflammation, and localized the potential treatment target to fetal conventional dendritic cell (cDC) progenitors. Here, we profile maternal OM-85 treatment-associated transcriptomic signatures in fetal bone marrow, and identify a series of immunometabolic pathways which provide essential metabolites for accelerated myelopoiesis.
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Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels.
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Innate Immune Training for Prevention of Recurrent Wheeze in Early ChildhoodPat Deborah Holt Strickland PhD, DSc, FRCPath, FRCPI, FAA PhD Emeritus Honorary Researcher Head, Pregnancy and Early Life Immunology Patrick.Holt@
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IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced ReprogrammingHigh risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high versus low susceptibility to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype.
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Single cell transcriptomics reveals cell type specific features of developmentally regulated responses to lipopolysaccharide between birth and 5 yearsHuman perinatal life is characterized by a period of extraordinary change during which newborns encounter abundant environmental stimuli and exposure to potential pathogens. To meet such challenges, the neonatal immune system is equipped with unique functional characteristics that adapt to changing conditions as development progresses across the early years of life, but the molecular characteristics of such adaptations remain poorly understood.