Where are we now in the CURE project?
CURE is now at a special moment, where interesting and relevant findings are arising. The project partners met online last 22nd of October for the annual meeting, to present their progress and discuss next steps. Due to the COVID-19 outbreak, the project has been granted a 6 month extension; March 2022 is the new date for the project’s completion.
The National and Kapodistrian University of Athens (N.K.U.A) and the Medical University of Lodz (MUL) followed asthmatic and healthy individuals over a one-year period to characterize microbiome dysbiosis, a condition defined by an imbalance of an individual’s microbiome. Researchers traced microbiome changes in the upper respiratory tract over time, alongside disease activity and immunological patterns, to investigate possible relationships.
During the visits, exposures, such as viral infections or allergens were registered, and respiratory samples were obtained for metagenomic analyses, host immune responses and phage isolation. Serum samples were taken for immunology assessment and plasma samples for total and specific IgE analyses.
The follow-up was finalised in February-March 2020 in both clinical centres. However, due to the COVID-19 pandemic, certain visits had to be cancelled and were performed after restrictive measures were lifted. Despite these accommodations, all the challenges related to COVID-19 were overcome.
The presence of bacteriophages contributes to a reduction of inflammation
The Swiss Institute of Allergy and Asthma Research (SIAF) and the Biomedical Research Foundation, Academy of Athens (BRFAA) are responsible for evaluating the immunological reactions and mechanisms of our body associated with microbial composition and effects of bacteriophage introduction in the airways.
Based on the above-mentioned samples collected by the clinical partners, BRFAA performed a detailed immune cell profiling using multiparametric flow cytometry. The immunological data was then shared with the University of Manchester to develop predictive mathematical models to understand the associations between asthma and microbiome composition in the lungs.
In addition, BRFAA also studied the effect of bacteriophages on blood cells’ ability to fight infection and adapt to intruders, also referred to as peripheral blood mononuclear cells (PBMC) viability. To test the effect, several phage preparations were introduced in cell culture models with a clinical isolate of Staphylococcus aureus from the nasopharynx of a 4-year-old male (resistant to penicillin and erythromycin). Data show that the presence of bacteriophages (from the commercial PYO cocktail by ELIAVA Institute) improved PBMC viability and reduced inflammation, as an immunological response against bacteria.
In parallel, SIAF examined the effects of bacteriophages on epithelial barrier integrity and on human innate lymphoid cells. It is of interest that bacteriophages, although they are viruses, do not attack or destroy the epithelium.
Taken together, these findings suggest that bacteriophages support the immune system without compromising human tissues; these are promising findings for a developing asthma treatment.
There is a strong evidence of a relationship between microbial dysbiosis and asthma
The University of Manchester (UMAN) is studying the microbial composition of the respiratory track and how it evolves over time, using metagenomics. Overall, there is good evidence of a correlation between microbiome dysbiosis and asthma. Considering the large variability of the metagenome, many factors influence its composition, such as geography and age. The question that is now being explored is how asthma influences the change of the metagenome over time.
Cooperation among partners is key for the success of the project
The Georgi Eliava Institute of Bacteriophagy, Microbiology and Virology (ELIAVA) and the ELIAVA Bio Preparations LTD (ELIBIO) are working together in order to isolate and generate a well-characterised collection of bacteriophages able to target bacteria associated with asthma.
ELIAVA has worked closely with other partners in the project to develop metagenomic and immunological analyses on the effects of bacteriophage on the body.
Every partner has unique capabilities to tackle different parts of the research. For example, UMAN received bacteriophages to study the phage-bacteria interaction. BRFAA received commercial Anti-staphylococcus and Pyo-bacteriophages, along with the corresponding placebo, for their work. Where appropriate, BRFAA collaborated with young scientists from the ELIAVA institute in Athens to explore host-phage interaction on PBMC cell cultures using invitro tissue. This extensive cooperation has been key to the early successes of the project.
A mathematical model to treat asthma is under development
All the work developed by the partners will enable the University of Manchester (UMAN) to develop and fit mathematical models to predict microbiome changes in the lungs after the introduction of bacteriophages, and thus help design clinical responses to treat asthma. The model is currently under development.