Modular antigen-translocation as a novel vaccine strategy for allergen-specific immunotherapy

The purpose of the present review is to describe recent approaches aimed at improving the treatment of allergic diseases through allergen-specific immunotherapy (SIT). Special emphasis will be given to the approach based on specific targeting of the major histocompatibility complex (MHC) class-II antigen-presentation pathway.

It is well recognized that IgE-mediated allergic diseases including rhinitis, atopic eczema and allergic asthma are increasing worldwide to a pandemic dimension. The only curative treatment remains allergen-SIT, which, however, requires a long treatment time of 3-5 years with up to 80 injections to confer protection. Recent findings strongly indicate that the treatment time and the number of injections could be drastically reduced by turning immunotherapy to a true vaccination. Direct injection of allergen extracts into the inguinal lymph nodes and targeting the MHC class-II antigen-presentation pathway by recombinant modular antigen-translocating vaccines have the potential to cure allergic diseases in a very short time.

The mechanisms of allergic inflammation can be divided into four distinct stages: T cell activation, organ-selective homing, survival/reactivation and effector functions. On the basis of this new knowledge several novel concepts aimed at treating allergic diseases have been developed. The area of allergen-SIT is experiencing exciting developments. Reciprocal regulation of effector and regulatory T cell subsets is being more and more used to develop novel strategies for immunomodulation.