Project 05

Rudolf Valenta, Dept. of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna.

Project 05: Towards prophylactic vaccination of allergy.

Rudolf Valenta has been working in the field of allergy research for more than 25 years. Starting with the molecular and immunological characterization of important allergens he continued to develop recombinant allergen-based diagnostic tests as well as therapeutic allergy vaccines based on recombinant allergens and genetically engineered hypoallergens and advanced them into clinical application. Within this project he wants to develop the ground for allergen-specific prophylactic strategies to prevent allergy. During the first project period Valenta and his team has obtained results which may have importance for finding allergen-specific prophylactic strategies against allergy. Using micro-arrayed allergens they have been able to study the transmission of allergen-specific IgG from the mother to the child as well as the evolution of the IgE and IgG response in early childhood. These studies showed that there is a time window of several years in childhood during which allergic IgE sensitizations can occur. Accordingly it seems that early postnatal forms of allergen-specific prophylactic strategies are needed. Furthermore, they have been able to identify two promising allergen-specific prophylactic strategies which they would like to investigate. One is based on immunization with non-allergenic, B cell epitope-containing allergen peptides fused to an allergen-unrelated carrier molecule which induces allergen-specific IgG preventing sensitization. The other strategy will use non-allergenic T cell epitope-containing peptides for oral tolerance induction. In the second period of the SFB program Valenta and his team plan a meticulous analysis of the humoral, cellular and cytokine responses in allergic patients who have been immunized with recombinant fusion proteins consisting of B cell epitope-containing peptides from the major grass pollen allergens fused to hepatitis B-derived PreS. These studies will include a detailed mapping of the epitope-specificities, avidities and blocking capabilities of allergen-specific IgG subclass responses on basophil activation and T cell activation. A special emphasis will be placed on the analysis of the IgE sensitization capacity of the allergen derivatives because it was found that immunization only induced allergen-specific IgG but did not boost allergen-specific IgE. In animal models it will be studied if immunization with the PreS-bound allergen-derived B cell epitopes or the administration of IgG antibodies of immunized patients can prevent and treat allergic sensitization.
In parallel strategies based on oral tolerance induction for preventing allergic sensitization with non-allergenic T cell epitope-containing peptides from the major birch pollen allergen, Bet v 1, the major grass pollen allergen, Phl p 5 and the major mugwort allergen, Art v 1 will be investigated in murine models. Goals of these experiments will be to find out if enteric coating of the peptides enhances the ability of the peptides to induce tolerance. Experiments will be conducted to determine how far the length of the peptides can be expanded to obtain tolerance, to avoid sensitization and to cover the allergen sequence with the fewest possible peptides. Different treatment schedules will be studied to find schedules which give sustained tolerance and the mechanisms of tolerance will be analyzed. 
The ultimate vision of these mechanistic studies is to provide the ground for the rational design of studies exploring if immunization with non-allergenic recombinant carrier-bound, allergen-derived B cell epitope containing peptides and/or oral tolerance induction with non-allergenic T cell epitope containing peptides can safely and effectively prevent allergy in humans.


valentaProf. Dr. Rudolf Valenta, MD
Division of Immunopathology
Department of Pathophysiology and Allergy Research
Center for Pathophysiology, Infectiology and Immunology
Medical University of Vienna
Waehringer Guertel 18-20
1090 Vienna, Austria
Phone: +43 1 40400 51080
Fax: +43 1 40400 51300
E-Mail: This email address is being protected from spambots. You need JavaScript enabled to view it.



Campana, R., S. Vrtala, B. Maderegger, P. Jertschin, G. Stegfellner, I. Swoboda, M. Focke-Tejkl, K. Blatt, A. Gieras, D. Zafred, A. Neubauer, P. Valent, W. Keller, S. Spitzauer, and R. Valenta*. 2010. Hypoallergenic derivates of the major birch pollen allergen Bet v 1 obtained by rational sequence reassembly. J. Allergy Clin. Immunol. 126:1024-1031; DOI: 10.10167j.jaci.2010.05.023

Linhart, B., and R. Valenta*. 2012. Vaccines for allergy. Curr Opin Immunol. 24: 354-60; DOI: 10.1016/j.coi.2012.03.006. Review.

Valenta, R.*, R. Campana, K. Marth, and M. van Hage. 2012. Allergen-specific immunotherapy: from therapeutic vaccines to prophylactic approaches. J Intern Med. 272: 144-57; DOI: 10.1111/j.1365-2796.2012.02556.x. Review Lupinek, C., K. Marth, V. Niederberger, and R. Valenta*. 2012. Analysis of serum IgE reactivity profiles with microarrayed allergens indicates absence of de novo IgE sensitizations in adults. J. Allergy Clin Immunol. Aug. 3; DOI: 10.1016/j.jaci.2012.06.028.

Marth, K., I. Breyer, M. Focke-Tejkl, K. Blatt, M. Shamji, J. Layhadi, A. Gieras, I. Swoboda, D. Zafred, W. Keller, P. Valent, S. Durham, and R. Valenta. A non-allergic birch pollen allergy vaccine consisting of hepatitis PreS-fused Bet v 1 peptides focuses blocking IgG towards IgE epitopes and shifts immune responses to a tolerogenic and Th1 phenotype. J. Immunol. In press.