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Babor, M.

Publications and source records attributed to Babor, M..

3 recordsLinked to original sources

A system-view of B. pertussis booster vaccine responses in adults primed with whole-cell vs. acellular vaccine in infancy

Whole-cell inactivated vaccine against Bordetella pertussis (wP) was substituted in many countries by an acellular subunit vaccine (aP) to reduce side effects. Recent epidemiological studies have shown that aP vaccination in infancy induces less durable immunity than wP vaccination. To determine immunological differences associated with aP vs. wP priming, we performed system-level profiling of the immune response in adults primed with aP vs. wP vaccine in infancy following the Tdap booster vaccination as a surrogate to antigen encounter in vivo. Shared immune responses across cohorts were identified, including an increase of the blood monocyte frequency on day 1, and strong antigen-specific IgG response seven days after boost. Comparing aP and wP primed individuals, we found a subset of aP-primed individuals with higher levels of expression for several genes including CCL3 on day 3 and NFKBIA and ICAM1 on day 7 post immunization. These observations were supported by increased CCL3 concentrations in plasma of aP primed individuals. Contrary to the wP individuals, the CCL3-high aP subset presented boosted PT-specific IgE responses. Furthermore, higher antigen specific IgG4 and IgG3 antibodies against specific vaccine antigens at baseline and post boost of aP individuals was observed, suggesting a long term maintained difference in the IgG subtype response. Overall our findings demonstrate that, while broad immune response patterns to Tdap boost overlap between aP and wP primed individuals, a subset of aP primed individuals present a divergent response. These findings provide candidate targets to study the causes and correlates of waning immunity after aP vaccination.

systems biology↗

A reference map of the human protein interactome

Global insights into cellular organization and function require comprehensive understanding of interactome networks. Similar to how a reference genome sequence revolutionized human genetics, a reference map of the human interactome network is critical to fully understand genotype-phenotype relationships. Here we present the first human \"all-by-all\" binary reference interactome map, or \"HuRI\". With ~53,000 high-quality protein-protein interactions (PPIs), HuRI is approximately four times larger than the information curated from small-scale studies available in the literature. Integrating HuRI with genome, transcriptome and proteome data enables the study of cellular function within essentially any physiological or pathological cellular context. We demonstrate the use of HuRI in identifying specific subcellular roles of PPIs and protein function modulation via splicing during brain development. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms underlying tissue-specific phenotypes of Mendelian diseases. HuRI thus represents an unprecedented, systematic reference linking genomic variation to phenotypic outcomes.

systems biology↗

No cell is an island: circulating T cell:monocyte complexes are markers of immune perturbations

Our results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artefacts and thus ignored in data acquisition and analysis, are the result of true biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell:monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be revisited.

immunology↗