This study investigates whether immersive virtual reality (VR) exposure to allergen-related stimuli can modulate behavioural, neurophysiological, psychophysiological, and immune responses in adults with bee or wasp venom allergy.

The study consists of two parts. In Part 1, adults with documented bee or wasp venom allergy and healthy volunteers will undergo immersive VR exposure in a realistic picnic environment. All participants will first be exposed to a control condition involving virtual flies. They will then be randomly assigned to exposure to either virtual bees or wasps or a control condition involving virtual flies. During the VR sessions, behavioural responses, heart rate and heart-rate variability, skin conductance, pupil dilation, temperature, and electroencephalographic activity will be recorded. Blood samples will be collected before and after VR exposure to assess changes in basophil activation and other immunological markers.

In Part 2, patients receiving standard-of-care venom immunotherapy will be followed longitudinally. Blood samples will be collected before and during treatment to characterize immunological changes associated with venom desensitization. After approximately six months of venom immunotherapy, participants will undergo a further VR session involving either virtual bees or wasps or virtual flies. Behavioural, psychophysiological, neurophysiological, and immunological assessments will be repeated to determine whether venom immunotherapy reduces responses to virtual allergen-related stimuli.

The primary outcome is the change in basophil activation, measured as the percentage of CD63-positive circulating basophils. Secondary outcomes include changes in circulating type 2 innate lymphoid cells and regulatory T cells, serum IL-13 and tryptase concentrations, reaction times, cardiovascular and autonomic responses, pupil dilation, skin temperature, and electroencephalographic responses.

The study does not involve exposure to real insects or venom as part of the investigational VR procedure. Its aim is to improve understanding of brain-immune interactions in allergy and to provide preliminary evidence for the potential future use of VR-based approaches alongside conventional allergy treatment.