Development of an mRNA vaccine targeting IgE for the treatment of allergic diseases – AllergyVACS2

The incidence of allergies has dramatically increased over the last three decades in industrialized countries, with an estimate of 15% to 30% allergic patients in Europe and the US. Moreover, the World Health Organization now estimates that half of the people will develop allergies by 2050. Despite this, there is still no efficient long-term therapy to treat allergies. Immunoglobulin-E (IgE) antibodies play a key role in allergic reactions. Indeed, diagnostic of allergies is largely based on the detection of allergen-specific IgE antibodies. IgE bind to their high-affinity receptor FceRI mainly expressed on the surface of mast cells and basophils. Upon contact with an allergen in allergic patients, such allergen is recognized by IgE on the surface of mast cells and basophils, leading to activation of these cells and release of mediators, among which histamine, responsible for allergy symptoms. Thus, IgE represent a key therapeutic target to treat allergy.

The main objective of the project ‘AllergyVACS2’ is to develop an mRNA vaccine against IgE, and provide a proof-of-concept of the safety and efficiency of this therapeutic vaccine. This vaccine should induce polyclonal responses against IgE. We will perform pharmacologic studies in animal models to demonstrate the safety and immunogenicity of this anti-IgE mRNA vaccine. The therapeutic benefit of the vaccine will be assessed using clinically-relevant models of anaphylaxis, the most dramatic allergic reaction. We expect to have identified a safe and efficient vaccine by the end of this grant, which would meet all criteria to be ready for initiation of clinical trials.