NOVARA · Novel Vaccines for Allergen-specific immunotherapy of Ragweed pollen Allergy

Ragweed pollen allergy is a new and steadily growing health problem in Europe. The aim of the proposed Marie Curie Fellowship, NOVARA, is to engineer hypoallergenic Amb a 1, the major allergen of ragweed pollen, for use as new vaccine candidates for allergen-specific immunotherapy (SIT). Since conventional SIT may induce undesired IgE-mediated side-effects, there is a need for well defined proteins with reduced or abolished IgE binding capacity and retained T cell-activating capacity, as substitutes for the highly variable natural allergen extracts. Hypoallergenic variants of Amb a 1 have not yet been fully explored. In particular, it is unclear which structural modifications of hypoallergens could improve their effectiveness for use as active components in allergy therapy with minimised risk of anaphylactic side effects and shorter treatment regimens. Thus, a number of hypoallergenic variants, with different sizes and folding status, will be produced within NOVARA and the most promising candidates will be fully characterized, including the analysis of primary structure, folding, surface exposed hydrophobic portions, aggregation status and stability. Human IgE reactivity, allergenicity and T cell responses will be investigated as indicative of their immunogenicity in humans. The in vivo capacity of the candidate vaccines to induce humoral and cellular responses will be evaluated in a murine model. The opportunity to acquire additional scientific skills in molecular biology and immunology, as well as dealing with intellectual property, ethical and management issues, will allow the Applicant to reach a position of professional maturity. NOVARA has industrial and clinical interests and further strengthens the EU research portfolio in the allergy field.