Screening potential allergy vaccine components

Rationale: Allergen immunotherapy (AIT) is the only disease-modifying treatment for IgE-mediated allergies, but the long treatment duration required (3-5 years) and the risk of potentially severe adverse events are major disadvantages that limit its application.

Objective: The objective of the study is to collect blood samples for generation of monocyte-derived DCs (moDCs) and to use these antigen-presenting cells to evaluate the immune-skewing potential of different combinations of nanoparticles, purified allergens, adjuvants and targeting reagents. The ultimate goal is to find combinations that increase safety (by lowering allergenic potency) and increase efficacy of induction of anti-inflammatory protective responses, both with respect to kinetics and effect size.

Study design: This is a non-interventional study in which blood samples are obtained to facilitate in vitro cellular analyses.

Study population: The study population consists of adult (18-65 yrs) allergic rhinitis subjects and two groups of adult subjects, i.e. non-allergic rhinitis subjects and healthy subjects.

Intervention (if applicable): Not applicable.

Main study parameters/endpoints: The main study parameter is successful generation of sufficient moDCs from (multiple) voluntary blood donations of minimally 50 ml to maximally 200 ml of fresh blood, from a total of 50 donors.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Subjects will contribute to increasing the knowledge in the field of innovation of AIT for the treatment of allergic diseases. In the future this may provide new safer and more effective treatments that benefit the allergic patient. Disadvantage and risks of participating are minimal. Blood drawing can cause a low level of pain and may occasionally result in a hematoma.

In the frame of three projects at Amsterdam UMC, we are exploring possibilities to improve AIT for both respiratory and food allergy. We have combined these three projects in a single protocol because experiments to be carried out with moDCs generated from the obtained blood samples will be used in identical experiments. In fact, candidate vaccine components from the three different projects can and will be compared in single experiments to establish which (combination of) approaches is most promising to improve AIT. One study focuses on the use of nanoparticles: liposomes of various composition and PLGA nanoparticles as alternative for aluminum hydroxide. By loading the liposomes/nanoparticles with allergen, it is shielded from contact with mast cells when injected, decreasing the risk of side-effects. The second study on the central hypothesis of the project is that sialylated antigens/allergens effectively induce a regulatory anti-inflammatory immune response, and the last on plant bioparticles that are expressing allergens on the surface and are rich in glycosylceramide which is thought to induce anti-inflammatory responses.

If the subject is prepared they can give 50-200 ml of blood on multiple occasions (up to maximally 20 times in 4 years)

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