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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - Born-Immune (Shaping of the Human Immune System by Primal Environmental Exposures In the Newborn Child)

Teaser

Summary

The project aims to investigate the development of the human immune system in newborn children. The project specifically aims to study the adaptive changes in human immune systems in response to early-life environmental factors such as the colonizing microbiome, food components, infections and vaccines. The project is important because newborn children are susceptible to infections, especially when born preterm, and vaccines are ideally given to newborn children but are not tailored to the unique functional properties of newborn immune systems, and finally, many immune-mediated diseases affecting individuals of all ages have been linked to environmental imprinting early in life in large population studies.

The overall objectives are to describe the changes occurring to the cell composition, function and phenotypes of immune cells in newborn children during their first months and years of life. Another key objective is to investigate the impact of diverse environmental exposures on these processes, such as mode of delivery, antibiotics, vaccines and breastfeeding vs formula-feeding.

The long-term implication of this work is that it can allow us to better care for all newborn children in order to minimize their risk of severe infections, optimize their responsiveness to vaccination and minimize their long-term risks of immune mediated diseases occurring, by improving the immune system priming and development.

Work performed

The project so far has been largely focused on patient enrollment and sample collection. We have developed novel strategies to preserve whole blood samples directly in the hospital, by clinical staff without research training, and with minimal handling and sample sparing methods. This now allow for us to preserve whole blood cells, by direct freezing without any manipulation, providing much more robust datasets that better reflect the in vivo situation of newborn immune systems. Combining this with optimized methods for plasma preservation, by immediate centrifugation after blood collection, we are able to analyze hundreds of plasma proteins, and all white blood cells from as little as 100 microliters of starting material, enabling samples to be analyzed even from the very sickest of preterm children.

In a first analysis we have revealed systems-level development of the newborn immune system in 100 newborn children during their first 100 days of life. This work was published in Cell in August 2018. In this analysis, we described a stereotypic pattern of change, shared by all preterm and term children, driven by microbial interactions on luminal surfaces.

In a second publication, currently in press in Nature Medicine, we have performed a global analysis of maternal IgG antibodies in the same cohort of newborn children. This paper shows that antibody-transfer during pregnancy occurs similarly in preterm and term children and that antibodies transferred as early as week 24 are equally protective against viruses such as RSV as antibodies transferred at full term.

Final results

The methods developed allow novel sampling schemes previously not available. These allow for more studies, previously not possible to perform due to complex sampling procedures and high blood volumes required for analysis. The knowledge gained throughout the project is also important and open novel areas of investigation for future studies that we are currently pursuing within the project.