Signal transduction and cellular responses induced by allergen immunotherapy

Allergic rhinitis is a major public health concern, affecting up to 28% of western populations, with a total cost of €960 per person per year in Sweden. Allergen immunotherapy (AIT) is the only method to change the course of allergic disease. Current standard of care is a three-year treatment of monthly injections or daily tablets.

Our work has shown that three injections of allergen into inguinal lymph nodes over 2 months modulate the adaptive immune response. We are currently running a phase III trial with 500 patients (EudraCT 2020-001060-28, BASEC Nr. 2021-02301). Given the success of our endeavours, we are becoming an international reference centre for ILIT.

Our proposal

We now seek to optimise our process and describe the cellular and molecular signal pathways initiated during this treatment by characterisation of the mechanisms activated during ILIT, primarily in man but also in animal models where necessary.

The mechanism of tolerance induction used in AIT is thought to depend on reactions in the lymph node after drainage of AIT allergen and adjuvant to the lymph node. However, this mechanism is not well characterised, cardinal limitations being (i) that the time of introduction of allergen into the lymph node is not accurately known, and (ii) that the small amount of allergen and adjuvant reaching the lymph node is insufficient for exploring the resulting immune signals. With ILIT, we can stimulate the human immune system in quantities that we will enable us to detect transduction signals within and between cells.

In collaboration we will evaluate the immune effects of ILIT on the innate (dendritic, innate lymphoid cells) and adaptive (T- and B-cells) tolerogenic immune responses in blood samples. Moreover, we should be able to detect signals in and between follicular dendritic, T- and B-cells in fine needle aspirates from the treated lymph nodes; we will also sample circulating plasma cells one week after injection of allergen. These cellular data will be compared with the clinical effect we monitor during the grass pollen season.

We collaborate with Zürich University, regarding analysis and planning of clinical trials and exploration of mechanisms, Luxembourg Institute of Health, on analysis of leucocytes with Gigasom and Cytof to understand the responses of cells and Imperial College, UK, on optimized sampling of patients and targeted analysis of the samples obtained in clinical trials for allergen immunotherapy.

The ideal fellow has a passion for tolerance induction, innovation and translational research.

Research experience in cellular allergy is an advantage, as is experience with analysis of large multicolour flow cytometry data sets and experience with analysis of single cell responses in man.

We excel at ILIT treatment and designing and performing investigator initiated clinical trials, but also have solid expertise in culture of mast cells, analysis of induced sputum and basophil activation testing.

We are very well connected to specialist centers. Aarhus University has state of the art core facilities that we collaborate with.

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