[Frontiers in Bioscience 14, 4606-4617, January 1, 2009]

Recombinant hypoallergens for immunotherapy of Parietaria judaica pollen allergy

Juan Andres Asturias

Bial-Aristegui, Research and Development Department, Alameda Urquijo, 27, E-48008 Bilbao, Spain

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Current allergen extracts for specific immunotherapy
4. Potential benefits and disadvantages of recombinant allergens
5. Strategies for the modification of recombinant allergens to improve SIT
5.1. Chemically modified allergens
5.2. Folding variants
5.3. Genetically modified allergens
5.3.1. Site-directed mutants
5.3.2. Deletion mutants
5.3.3. Allergen fragments
5.3.4. Allergen oligomers
5.3.5. Allergen fusions
5.3.6. Chimeras: allergen hybrids and shuffled molecules
6. Recombinant hypoallergens from Parietaria judaica
6.1. Rationale
6.2. Design
6.3. Reduced IgE binding and allergenic activity of recombinant hybrid proteins
6.3.1. Western blotting
6.3.2. IgE-binding activity
6.3.3. Skin prick reactivity
6.4. T-cell reactivity of recombinant hybrid proteins
7. Conclusions
8. Future Perspectives
9. Acknowledgements
10. References

1. ABSTRACT

Recombinant allergens are a promising alternative to crude allergen extracts for diagnosis and therapy of allergic diseases. Genetically modified allergen derivatives with reduced allergenic activity but retaining their immunogenicity have also been produced to increase safety and specificity of allergen-specific immunotherapy. When a limited number of allergens are responsible for most of the allergenic activity, fusion proteins comprising these major allergens can be used to simplify vaccine development. Three different allergen fusions of Par j 1 and Par j 2, the major allergens from Parietaria judaica, were characterized. Two of them (Q1 and Q2) showing reduced allergenicity but conserved immunogenicity represent suitable candidates for allergen-specific immunotherapy against P. judaica pollen allergy.