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The developing immune system and allergy

Early aberrant antibody responses of aeroallergen sensitised people to subclinical bacterial infection

Early aberrant antibody responses, aeroallergen sensitised people, subclinical bacterial infection

Professor Wayne Thomas

Honorary Emeritus Fellow; Scientific Reviewer - Animal Ethics

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

Appropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group.

Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4

Previous 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.

Innate Immune Training for Prevention of Recurrent Wheeze in Early Childhood

Pat Deborah Holt Strickland PhD, DSc, FRCPath, FRCPI, FAA PhD Emeritus Honorary Researcher Head, Pregnancy and Early Life Immunology Patrick.Holt@

IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming

High 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.

Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85

Incomplete 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.

OPTIMUM study protocol: an adaptive randomised controlled trial of a mixed whole-cell/acellular pertussis vaccine schedule

Combination 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.

Transplacental Innate Immune Training via Maternal Microbial Exposure: Role of XBP1-ERN1 Axis in Dendritic Cell Precursor Programming

We 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.