Allergy Immunotherapy

The only specific and disease-modifying form of therapy is allergen-specific immunotherapy (SIT) , a therapeutic vaccination based on the administration of the disease eliciting allergens to the allergic patient. SIT using extracts from natural allergen sources was first described by Noon et al. in 1911. Vaccination with allergen extracts is frequently accompanied by unwanted side effects which may be life-threatening such as anaphylactic shock. 

Therefore, the majority of allergic patients today are still treated with pharmacotherapy (e.g. antihistamines) which alleviates the symptoms of allergy but cannot stop the progression of the disease (allergic march). There is an urgent medical need for innovative products for SIT with an advanced safety profile and defined/controlled composition to meet state-of-the-art pharmaceutical standards. 



Biomay's Pipeline for Immunotherapy of Allergic Diseases

Biomay has assembled an impressive pipeline of innovative products for immunotherapy of allergic diseases based on its proprietary technology platforms.

The IgE immune apheresis device IgEnio®, co-developed with Fresenius Medical Care, has achieved CE mark designation and is currently actively marketed in several European countries. Additional clinical studies are underway to broaden the scope of applications for this unique product.

The most advanced peptide carrier fusion allergy vaccine BM32, indicated for grass pollen allergy, has completed phase IIb of clinical development and is ready for phase III pivotal Trials.



Allergy Products

Peptide Carrier Fusion Vaccines (PCFiT Technology)

Peptide carrier fusion vaccines are the current focus for allergy immunotherapy research and development at Biomay. 

Peptide carrier fusion vaccines contain linear peptides which are parts of B-cell epitopes. These peptides are fused to an immunogenic carrier element and expressed as fusion proteins by recombinant technology. Peptide carrier fusion vaccines induce a focussed allergen specific IgG response that is directed against parts of the IgE epitope and block the binding of IgE. 

Peptide carrier fusion vaccines offer superior efficacy and safety. They provide a universal, highly specific allergy immunotherapy platform with an unrivaled safety profile. The technology has been trademarked as PCFiT™ (Peptide Carrier FusIon Technology)

On the basis of convincing pre-clinical proof-of-concept and human data Biomay has completed an early stage clinical development program with its lead product BM32, a peptide carrier fusion vaccine against grass pollen allergies. This comprehensive program consisted of a Phase I safety study with skin testing and a study with controlled exposure to grass pollen in an environmental exposure chamber following immunization with BM32. The most important element of this program was a recently completed Phase IIb study with patients under natural pollen exposure. The results of this study constitute clinical proof of concept for BM32 and validation for the technology platform. PCFiT constructs for house dust mite (BM35) and ragweed vaccines (BM34) have been optimized for maximal coverage of allergens important for causing symptoms in patients. All peptide carrier fusion vaccines also including BM31 for birch pollen allergy are currently at the preclinical development stage. Future developments comprise Japanese cedar vaccines and cockroach vaccines. 

Biomay's proprietary technologies are well protected by a large and growing portfolio of patents and patent applications. For manufacturing its peptide carrier fusion vaccines, Biomay utilizes state of the art technology in its in house GMP facility. 

Leitet Herunterladen der Datei einPeptide Carrier Fusion, PDF ~ 225 KB

You can watch an animated Video, which describes the mechanism of action under the following link:



Results of Clinical Trials with BM32

BM32 has no allergenic effect
BM32 alleviates allergic reaction in the pollen chamber
BM32 improves allergy symptoms during the pollen season
BM32 improves quality of life in the pollen season

In order to confirm safety and efficacy of our grass pollen allergy vaccine BM32, four clinical trials have been completed in phase I and II.


In phase I (CS-BM32-001), it was demonstrated that BM32 had no appreciable IgE dependent and T-cell dependent allergenic effect, when it was applied in skin testing and atopy patch testing.  


In phase IIa (CS-BM32-002), BM32 significantly reduced allergic symptoms, measured by total nasal symptom score (TNSS) upon provocation with grass pollen for six hours in a pollen chamber. 


In the first phase IIb study (CS-BM32-003), the optimal dose of BM32 was determined to be 20 μg per allergen component. This dose reduced a combined score of allergic symptoms and consumption of allergy relief medication by >20% and allergy symptoms by 29%. In addition, patients' quality of life was significantly improved over two allergy seasons.


In the second phase IIb trial (CS-BM32-004), a dose regimen of five injections of 20 μg BM32 was found to give optimal protection from grass pollen allergy in the first season of treatment.


In all studies, BM32 was found to be very safe and extremely well tolerated.


The detailed results of these studies can be found under the following links:


 CS-BM32-001 (phase I)

CS-BM32-002 (phase IIa)

CS-BM32-003 (phase IIb)

CS-BM32-004 (phase IIb)



Key publications

The scientific approach of Biomay and its network to allergy-specific immunotherapy is published in numerous peer-reviewed articles. Below, the summary of the most significant and up-to-date papers proves the expertise of Biomay´s network and the relevance of its technology.

Find references to following topics:

Allergy Immunotherapy / Reviews and Mechanistic Studies Reviews

Campana, R., Huang, H.-J., Freidl, R., Linhart, B., Vrtala, S., Wekerle, T., Karaulov, A., Valenta, R. (2017) Recombinant allergen and Peptide-based approaches for allergy prevention by oral tolerance, Semin. Immunol. (in press,  

Valenta, R., Campana, R., Focke-Tejkl., M., Niederberger, V. (2016) Vaccine development for allergen-specific immunotherapy based on recombinant Allergens and synthetic allergen Peptides: Lessons for the past and novel mechanisms of Action for the future J. Allergy Clin. Immunol. 137: 351-357

Marth, K., Focke-Teijkl, M., Lupinek, C., Valenta, R., Niederberger, V. (2014). Allergen peptides, recombinant Allergens and hypoallergens for allergen-specific immunotherapy. Curr. Treat. Options Allergy 26: 91-106

Focke-Tejkl, M., Valenta R. (2012) Safety of engineered allergen-specific immunotherapy vaccines. Curr. Opin. Allergy Clin. Immunol. 12: 555-565

Linhart, B., Valenta R.(2012) Vaccines for allergy. Curr. Opin. Immunol. 24: 253-262

Valenta, R., Coffman R.L. (2011) Current strategies for allergen-specific immunotherapy. Curr. Top. Microbiol. Immunol. 352:v-vi

Edlmayr J., Niespodziana K, Fock-Tejkl, M., Linhart, B., Valenta, R. (2011)  Allergen-specific immunotherapy: towards combination vaccines for allergic and infectious diseases. Curr. Top. Micobiol. Immunol. 352: 121-140

Valenta, R., Niespodziana, K., Focke-Tejkl, M., Linhart, B., Marth, K., Huber, H., Neubauer, A., Niederberger V. (2011) Recombinant Allergens: what does the future hold? J. Allergy Clin. Immunol. 127: 860 ff.

Valenta, R., Linhart, B., Swoboda, I., Niederberger, V. (2011) Recombinant Allergens for allergen-specific immunotherapy: 10 years anniversary of immunotherapy with recombinant Allergens. Allergy 66: 775-783

Valenta, R., Ferreira, F., Focke-Tejkl, M., Linhart, B., Niederberger, V., Swoboda, I., Vrtala, S. (2010)From allergen genes to allergy vaccines. Ann. Rev. Immunol. 28: 211-241

Focke M., Swoboda, I., Marth, K., Valenta, R.(2010) Developments in allergen-specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen-specific immunoglobulin E and T cell reactivity. Clin. Exp. Allergy 40: 385-397

Bohle, B. (2008). T cell responses during allergen-specific immunotherapy of Type I allergy. Front. Biosci. 13: 6079-6085.

Valenta, R. and Niederberger, V. (2007). Recombinant allergens for immunotherapy. Allergy Clin. Immunol. Vol. 119/4: 826-830.

Wallner, M., Briza, P., Thalhamer, J. and Ferreira, F. (2007). Specific immunotherapy in pollen allergy. Curr. Opin. Mol. Ther. 9: 160-167. Review.

Larché, M., Akdis C.A. and Valenta, R. (2006). Immunological mechanisms of allergen-specific immunotherapy. Nature Reviews Immunology 6, 761-771. 

Ferreira, F., Briza, P., Inführ, D., Schmidt, G., Wallner, M., Wopfner, N., Thalhamer, J. and Achatz, G. (2006). Modified recombinant allergens for safer immunotherapy. Inflamm. Allergy Drug Targets 5(1): 5-14. Review. 

Niederberger, V., Valenta, R. (2004). Recombinant allergens for immunotherapy. Where do we stand? Curr. Opin. Allergy Clin. Immunol. 4, 549-554. 

Valenta, R., Ball, T., Focke, M., Linhart, B., Mothes, N., Niederberger, V., Spitzauer, S., Swoboda, I., Vrtala, S., Westritschnig, K. and Kraft, D. (2004). Immunotherapy of allergic diseases. Adv. Immunol. 82, 105-153.

Valenta, R. and Kraft, D. (2002). From allergen structure to new forms of allergen-specific immunotherapy. Curr. Opin. Immunol. 14, 718-727.

Ferreira, F., Wallner, M., Breiteneder, H., Hartl, A., Thalhamer, J. and Ebner, C. (2002). Genetic engineering of allergens: Future therapeutic products. Int. Arch. Allergy Immunol. 128: 171-178. Review.

Valenta, R. (2002). The future of antigen-specific immunotherapy of allergy. Nature Reviews Immunology 2: 446 -453.

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Mechanistic Studies

Curin, M., Garmatiuk, T., Resch-Marat, Y., Chen, KW., Hofer, G., Fauland, K., Keller, W., Hemmer, W., Vrtala, S., Focke-Tejkl, M., Valenta, R. (2018) Similar localization of conformational IgE epitopes on the house dust mite Allergens Der p 5 and Der p 21 despite limites IgE-cross-reactivity Allergy (in press, doi: 10.1111/all.13398)

Göbl, C., Focke-Tejkl, M., Najafi, N., Schrank, E., Madl, T., Kosol, S., Madritsch, C., Dorofeeva, Y., Flicker, S., Thalhamer, J., Valenta, R., Zangger, K., Tjandra, N. (2017) Flexible IgE epitope-containing Domains of Phl p 5 cause high allergenic activity J. Allergy Clin. Immunol. 140: 1187-1191

Selb., R., Eckl-Dorna, J., Neunkirchner, A., Schmetterer, K., Marth, K., Gamper, J., Jah-Schmid, B., Pickl, W.F., Valenta, R., Niederberger, V. (2017) CD23 Surface density on B-cells is associated with IgE Levels and determines IgE-facilitated allergen uptake, as well as activation of allergen-specific T cells J. Allergy Clin. Immunol. 139:290-299

Selb, R., Eckle-Dorna, J., Twaroch, T.E., Lupinek, C., Teufelberger, A., Hofer, G., Focke-Tejkl, M., Gep, B., Linhart, B., Breiteneder, H., Ellinger, A., Keller, W., Roux, K.H., Valenta, R., Niederberger, V. (2017) Critical and direct involvement of the CD23 stalk Region in IgE binding J. Allergy Clin. Immunol. 139: 281-289

Gieras, A., Linhart, B., Roux. K.H., Dutta, M., Khodoun, M., Zafred, D., Cabauatan, C.R., Lupinek, C., Weber, M., Focke-Tejkl., M., Keller, W., Finkelman, F.D., Valenta, R. (2016) IgE epitope proximity determines immun complex shape and effector cell activation capacity J. Allergy Clin Immunol. 137: 1557-1565

Focke-Tejkl, M., Campana, R., Reininger, R., Lupinek, C., Blatt, K., Valent, P., Pavkov-Keller, T., Keller, W,, Valenta, R.(2014) Dissection of the IgE and T-cell recognition of the Major Group 5 grass pollen allergen Phl p 5. J Allergy Clin Immunol. 133:836-45

Linhart, B., Narayanan, M., Focke-Tejkl, M., Wrba, F., Vrtala, S., Valenta, R. (2014) Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides laccking allergen-specific T cell epitopes reduces Bet v 1 specific t cell Responses vial blocking antibodies in a murine model for birch pollen allergy. Clin Exp. Allergy 44: 278-287

Linhart, B., Valenta, R. (2012) Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives. Vaccine 30:4328-4335

Dall'Antonia, F., Gieras, A., Devanaboyina, S.C., Valenta, R. Keller, W.(2011) Prediction of IgE-binding epitopes by means of allergen surface comparison and correlation to cross-reactivity. J. Allergy Clin. Immunol. 128: 872-879

Gieras, A., Cejka, P., Blatt, K, Focke-Tejkl, M., Linhart, B., Flicker, S., Stoecklinger, A., Marth, K., Drescher, A., Thalhamer, J., Valent, P., Majdic, O., Valenta, R. (2011) Mapping of conformational IgE epitopes with Peptide-specific monoclonal antibodies revels simultaneous binding of different IgE antibodies to a surface patch on the major birch pollen allergen Bet v 1. J. Immunol. 186:5333-5344

Campana, R., Vrtala, S., Maderegger, B., Dall'Antonia, Y., Zafred, D, Blatt, K., Herrmann, H., Focke-Tejkl, M., Swoboda, I., Scheiblhofer, S., Giera, A., Neubauer, A., Keller, W., Valent, P., Thalhamer, J., Spitzauer, S., Valenta, R. (2011) Altered IgE epitope presentation: a model for hypoallergenic activity revealed for Bet v 1 trimer. Mol. Immunol. 48: 431-441

Pree, I., Shamji, M.H., Kimber, I., Valenta, R., Durhan, S.R., Niederberger, V. (2010) Inhibition of CD23-dependent facilitated allergen binding to B cells following vaccination with genetically modified hypoallergenic Bet v 1 molecules. Clin. Exp. Allergy 40:1346-1352

Campana, R., Mothes, N., Rauter, I., Vrtala, S., Reininger, R., Focke-Tejkl, M., Lupinek, C., Balic, N., Spitzauer, S. and Valenta, R. (2008). Non-IgE-mediated chronic allergic skin inflammation revealed with rBet v 1 fragments. J. Allergy Clin. Immunol.  121, 528-530.

Rauter, I., Krauth, M.T., Westritschnig,  K., Horak, F., Flicker, S., Gieras, A., Repa, A., Balic, N., Spitzauer, S., Huss-Marp, J., Brockow, K., Darsow, U., Behrendt, H., Ring, J., Kricek, F., Valent, P. and Valenta, R. (2008). Mast cell derived proteases control allergic inflammation through cleavage of IgE. J. Allergy Clin. Immunol. 121, 197-202. 

Bohle, B., Kinaciyan, T., Gerstmayr, M., Radakovics, A., Jahn-Schmid, B. and Ebner, C. (2007). Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T cell tolerance and immune deviation. J. Allergy Clin. Immunol. 120: 707-713.

Kinaciyan, T., Jahn-Schmid, B.,  Radakovics, A., Zwölfer, B., Schreiber, C., Francis, J.N., Ebner, C. and Bohle, B. (2007). Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1-homolog Mal d 1. J. Allergy Clin. Immunol. 119: 937-943.

Linhart, B., Bigenzahn, S., Hartl, A., Lupinek, C., Thalhammer, J., Valenta, R. and Wekerle, T. (2007). Costimulation blockade inhibits allergic sensitization but does not affect established allergy in a murine model of grass pollen allergy. J. Immunol. 178, 3924-3931.

Jahn-Schmid, B., Fischer, G., Bohle, B., Fae, I, Gadermaier, G., Dedic, A., Ferreira, F. and Ebner, C. (2005). Antigen presentation of the immunodominant T cell epitope of the major mugwort pollen allergen, Art v 1, is associated with the expression of HLA-DRB1*01. J. Allergy Clin. Immunol. 115: 399-404.

Mothes, N., Heinzkill, M., Drachenberg, K.J., Sperr, W.R., Krauth, M.T., Majlesi, Y., Semper, H., Valent, P., Niederberger, V., Kraft, D. and Valenta, R. (2003). Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies. Clin. Exp. Allergy 33, 1198-1208.

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Clinical Trials with Recombinant Allergens and Allergen Derivatives

Pauli, G., Larsen, T.H., Rak, S., Horak, F., Pastorello, E., Valenta, R., Purohit, A., Arvidsson, M., Lavina, A., Schröder, J.W., Luksch, N., Spitzauer, S., Armelle S., Montagut, S., Galvain, S., Melac, M., André, C., Poulsen, L.K. and Malling, H.J. (2008). Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis. J. Allergy Clin. Immunol. 122, 951-960.

Westritschnig, K.,  Horak, F., Swoboda, I., Barlic, N., Spitzauer, S., Kundi, M., Fiebig, H., Suck, R., Chromwell, O. and Valenta, R. (2008). Different allergenic activity of grass pollen allergens revealed by skin testing. Eur. J. Clin. Invest. 38, 260-267.

Pree, I., Reisinger, J., Focke, M., Vrtala, S., Pauli, G., van Hage, M., Cromwell, O., Gadermaier, E., Egger, C., Reider, N., Horak, F., Valenta, R. and Niederberger, V. (2007). Analysis of epitope-specific immune responses induced by vaccination with structurally folded and unfolded recombinant Bet v 1-derivatives in man. J. Immunol., 179, 5309-5316.

Metz-Favre, C., Linhart, B., Focke-Tejkl, M., Purohit, A., de Blay, F., Valenta, R. and Pauli, G. (2007). Skin test diagnosis of grass pollen allergy with recombinant hybrid molecule. J. Allergy Clin. Immunol. . 120, 315-321.

Niederberger, V., Reisinger, J., Valent, P., Krauth, M.T., Pauli, G., van Hage, M., Cromwell, O., Horak, F. and Valenta, R. (2007). Vaccination with genetically modified birch pollen allergens: immune and clinical effects on oral allergy syndrome. J. Allergy Clin. Immunol. 119, 1013-1016.

Reisinger, J., Horak, F., Pauli, G., van Hage, M., Cromwell, O., König, F., Valenta, R. and Niederberger, V. (2005). Allergen-specific IgG antibodies in nasal secretions induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J. Allergy Clin. Immunol. 116, 347-354.

Niederberger, V., Horak, F., Vrtala, S., Spitzauer, S., Krauth, M.T., Valent, P., Reisinger, J., Pelzmann, M., Hayek, B., Kronquist, M., Gavelin, G., Grönlund, H., Purohit, A., Suck, R., Fiebig, H., Cromwell, O., Pauli, G., van Hage-Hamsten, M. and Valenta, r. (2004). Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc. Natl. Acad. Sci. USA  101 Suppl 2, 14677-14682.

Niederberger, V., Stübner, P., Spitzauer, S., Kraft, D., Valenta, R., Ehrenberger, K. and Horak, F. (2001). Skin test results but not serology reflect immediate type respiratory sensitivity: A study performed with recombinant allergen molecules. J. Invest. Dermatol. 117, 848-851.

Pauli, G., Purohit, A., Oster, J.P., de Blay, F., Vrtala, S., Niederberger, V., Kraft, D. and Valenta, R. (2000). Comparison of genetically engineered hypoallergenic rBet v 1 derivates with rBet v 1 wildtype by skin prick and intradermal testing: Results obtained in a french population. Clin. Exp. Allergy 30, 1076-1084.

Nopp, A., Halldén, G., Lundahl, J., Johansson, E., Vrtala, S., Valenta, R., Grönneberg, R. and van Hage-Hamsten, M. (2000). Comparison of inflammatory responses to genetically engineered hypoallergenic derivatives of the major birch pollen allergen Bet v 1 and to rBet v 1 wild type in skin chamber fluids collected from birch pollen allergic patients. J. Allergy Clin. Immunol. 106, 101-109.

Heiss, S., Mahler, V., Steiner, R., Spitzauer, S., Schweiger, C., Kraft, D. and Valenta, R. (1999). Component-resolved diagnosis (CRD) of Type I allergy with recombinant grass and tree pollen allergens by skin testing. J. Invest. Dermatol. 113, 830-837.

van Hage-Hamsten, M., Kronqvist, M., Zetterström, O., Johansson, E., Niederberger, V., Vrtala, S., Grönlund, H. and Valenta, R. (1999). Skin test evaluation of genetically engineered hypoallergenic derivates of the major birch pollen allergen, Bet v 1. Results obtained with a mix of two recombinant Bet v 1 fragments and rBet v 1 trimer in a swedish population before the birch pollen season. J. Allergy Clin. Immunol. 104, 969-977.

Pauli, G., Oster, J., Deviller, P., Heiss, S., Bessot, J., Susani, M., Ferreira, F., Kraft, D. and Valenta, R. (1996). Skin testing with recombinant allergens rBet v 1 and rBet v 2. Diagnostic value for birch pollen and associated allergies. J. Allergy Clin. Immunol. 97, 1100-1109.

Menz, G., Dolecek, C., Schönheit-Kenn, U., Ferreira, F., Moser, M., Schneider, T., Suter, M., Boltz-Nitulescu, G., Ebner, C., Kraft, D. and Valenta, R. (1996). Serological and skin-test diagnosis of birch pollen allergy with recombinant Bet v 1, the major birch pollen allergen. Clin. Exp. Allergy 26, 50-60.

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Recombinant Allergens - Characterization

Weghofer, M., Grote, M., Resch, Y., Casset, A., Kneidinger, M., Kopec, J., Thomas W.R., Fernández-Caldas, E., Kabesch, M., Ferrara, R., Mari, A., Purohit, A., Pauli, G., Horak, F., Keller, W., Valent, P., Valenta, R., Vrtala, S. (2013) Identification of Der p 23, a peritrophin-like protein, as a new major Dermatophagoides pteronyssinus allergen associated with the peritrophic matrix of mite fecal pellets. J Immunol. 190:3059-3067

Himly, M., Nony, E., Chabre, H., Van Overtvelt, L., Neubauer, A., van Ree, R., Buchheit, K.H., Vieths, S., Moingeon, P. and Ferreira, F. (2009). Standardization of allergen products: 1. Detailed characterization of GMP-produced recombinant Bet v 1.0101 as biological reference preparation. Allergy. Jan 29. [Epub ahead of print].

Klinglmayr, E., Hauser, M., Zimmermann, F., Dissertori, O., Lackner, P., Wopfner, N., Ferreira, F. and Wallner, M. (2009). Identification of B-cell epitopes of Bet v 1 involved in cross-reactivity with food allergens. Allergy  Jan 9 [Epub ahead of print].

Padavattan, S. , Flicker, S., Schirmer, T., Madritsch, C., Randow, S., Reese, G., Vieths, S., Lupinek, C., Ebner, C., Valenta, R. and Markovic-Housley, Z. (2009). High-affinity IgE recognition of a conformational epitope of the major respiratory allergen Phl p 2, as revealed by X-ray crystallography. J. Immunol.  (in press.)

Wallner, M., Erler, A., Hauser, A., Klinglmayr, M., Gadermaier, G., Vogel, L., Mari, A., Bohle, B., Briza, P. and Ferreira, F. (2009). Immunologic characterization of isoforms of Car b 1 and Que a 1, the major hornbeam and oak pollen allergens. Allergy Jan 17 [Epub ahead of print].

Chapman, M.D., Ferreira, F., Villalba, M., Cronwell, O., Bryan, D., Becker, W.F., Fernandez-Rivas, M., Durham, S., Vieths, S., Van Ree, R. and the CREATE consortium. (2008). Executive Summary: The European Union CREATE project to develop purified allergen standards as certified reference materials for allergenic products. J. Allergy Clin. Immunol. 122(5): 882-889.

Van Ree, R. et al. (2008). The CREATE Project: Development of Certified Reference Materials for Allergenic Products and Validation of Methods for their Quantification. Allergy 63(3): 310-326. Review.

Verdino, P., Barderas, R., Villalba, M., Westritschnig, K., Valenta, R., Rodriguez R. and Keller, W. (2008). Three-dimensional structure of the cross-reactive pollen allergen Che a 3: visualizing cross-reactivity on the molecular surfaces of weed, grass and tree pollen allergens. J. Immunol. 180: 2313-2321.

Wopfner, N., Gruber, P., Wallner, M., Briza, P., Ebner, C., Mari, A., Richter, K., Vogel, L. and Ferreira, F. (2008). Molecular and immunological characterization of novel weed pollen pan-allergens. Allergy 63: 872-881.

Padavattan, S., Schirmer, T., Schmidt, M., Akdis, C., Valenta, R., Mittermann, I., Soldatova, L., Slater, J., Mueller, U. and Markovic-Housley, Z. (2007). Identification of a B-cell epitope of hyaluronidase, a major bee venom allergen, from ist crystal structure in complex with a specific Fab. J. Mol. Biol. 368: 742-745.

Wopfner, N., Dissertori, O., Ferreira, F. and Lackner, P. (2007). Calcium-binding proteins and their role in allergic diseases. Immunol. Allergy Clin. North Amer. 27: 29-44. Review.

Wopfner, N., Bauer, R., Thalhamer, J., Ferreira, F. and Chapman, M. (2007). Immunologic analysis of monoclonal and IgE antibody epitopes on natural and recombinant Amb a 1. Clin. Exp. Allergy 38: 219-226.

Asero, R., Wopfner, N., Gruber, P., Gadermaier, G. and Ferreira, F. (2006). Artemisia and ambrosia hypersensitivity: co-sensitisation or co-recognition? Clin. Exp. Allergy 36: 658-665.  

Egger, M., Mutschlechner, S., Wopfner, N., Gadermaier, G., Briza, P. and Ferreira, F. (2006). Pollen-food-syndromes associated with weed pollinosis. Allergy 61: 461-476. Review.

Batard, T., Didierlaurent, A., Chabre, H., Mothes, N., Bussieres, L., Bohle, B., Couret, M.N., Ball, T., Lemoine, P., Focke-Teijkl, M., Chenal, A., Clement, G., Dupont, F., Valent, P., Krauth, M.T. , Andre, C., Valenta, R. and Moingeon, P. (2005). Characterization of Wild-Type Recombinant Bet v 1a as a Candidate Vaccine against Birch Pollen Allergy. Int. Arch. Allergy Immunol. 136: 239-249.

Leonard, R., Petersen, B.O., Himly, M., Kaar, W., Wopfner, N., Kolarich, D., van Ree, R., Ebner, C., Duus, J.O., Ferreira, F. and Altmann, F. (2005). Two novel types of O-glycans on the mugwort pollen allergen Art v 1 and their role in antibody binding. J. Biol. Chem. 280: 7932-7940.

Wopfner, N., Gadermaier, G., Egger, M., Asero, R., Ebner, C., Jahn-Schmidt, B. and Ferreira, F. (2005). The spectrum of allergens in ragweed and mugwort pollen. Int. Arch. Allergy Immunol. 138: 337-346. Review.

Gadermaier, G., Dedic, A., Obermeyer, G., Frank, S., Himly, M. and Ferreira, F. (2004). Biology of weed pollen allergens. Current Allergy and Asthma Rep. 4: 391-400. Review.

Neudecker, P., Nerkamp, J., Eisenmann, A., Nourse, A., Lauber, T., Schweimer, K., Lehmann, K., Ferreira, F. and Rösch, P. (2004). Solution structure, dynamics, and hydrodynamics of the calcium-bound cross-reactive birch pollen allergen Bet v 4 reveal a canonical monomeric two EF-hand assembly with a regulatory function. J. Mol. Biol. 336: 1141-1157.  

Pittner, G., Vrtala, S., Thomas, W.R., Weghofer, M., Kundi, M., Horak, F., Kraft, D. and Valenta, R. (2004). Component-resolved diagnosis of house-dust mite allergy with purified natural and recombinant mite allergens. Clin. Exp. Allergy 34: 597-603.

Swoboda, I., Grote, M., Verdino, P. Keller, W., Singh, M.B., De Weerd, N., Sperr, W.R., Valent, P., Balic, N., Reichelt, R., Suck, R., Fiebig, H., Valenta, R. and Spitzauer, S. (2004). Molecular characterization of polygalacturonases as grass pollen-specific marker allergens: Expulsion from pollen via submicronic respirable particles. J. Immunol. 172: 6490-6500.

Himly, M., Jahn-Schmid, B., Dedic, A., Kelemen, P., Wopfner, N., Altmann, F., van Ree, R., Briza, P., Richter, K., Ebner, C. and Ferreira, F. (2003). Art v 1, the major allergen of mugwort pollen, is a modular glycoprotein with a defensin-like and a hydroxyproline-rich domain. FASEB J. 17(1): 106-108.

Jahn-Schmid, B., Kelemen, P., Himly, M., Bohle, B., Fischer, G., Ferreira, F. and  Ebner, C. (2002). The T cell response to Art v 1, the major mugwort pollen allergen, is dominated by one epitope. J. Immunol. 169: 6005-6011.

Swoboda, I.,  Bugajska-Schretter, A., Verdino, P., Keller, W., Sperr, W.R., Valent, P., Valenta, R. and Spitzauer, S. (2002). Recombinant carp parvalbumin, the major cross-reactive fish allergen: A tool for diagnosis and therapy of fish allergy. J. Immunol. 168: 4576-4584.

Valenta, R. and Kraft, D. (2002). From allergen structure to new forms of allergen-specific immunotherapy. Curr. Opin. Immunol. 14: 718-727.

Verdino, P., Westritschnig, K., Valenta, R. and Keller, W. (2002). The cross-reactive calcium-binding pollen allergen, Phl p 7, reveals a novel dimer assembly. EMBO J. 21: 5007-5016.

Valenta, R. and Kraft, D. (2001). Recombinant allergen molecules: tools to study effector cell activation. Immunol. Rev. 179: 119-127.

Vrtala, S., Fischer, S., Grote, M., Vangelista, L., Pastore, A., Sperr, W.R., Valent, P., Reichelt, R., Kraft, D. and Valenta, R. (1999). Molecular, immunological, and structural characterization of Phl p 6, a major allergen and P-particle-associated protein from timothy grass (Phleum pratense) pollen. J. Immunol. 163: 5489-5496.

Ball, T., Fuchs, T., Sperr, W.R., Valent, P., Vangelista, L., Kraft, D. and  Valenta, R. (1999). B cell epitopes of the major timothy grass pollen allergen, Phl p 1, revealed by gene fragmentation as candidates for immunotherapy. FASEB J. 13: 1277-1290.

Niederberger, V., Hayek, B., Vrtala, S., Laffer, S., Twardosz, A., Vangelista, L., Sperr, W.R., Valent, P., Rumpold, H., Kraft, D., Ehrenberger, K., Valenta, R., and Spitzauer, S. (1999). Calcium-dependent immunoglobulin E recognition of the apo- and calcium-bound form of a crossreactive two EF-hand timothy grass pollen allergen, Phl p 7. FASEB J. 13: 843-856.

Hayek, B., Vangelista, L., Pastore, A., Sperr, W.R., Valent, P., Vrtala, S., Niederberger, V., Twardosz, A., D. Kraft, D. and Valenta, R. (1998). Molecular and immunological characterization of a highly cross-reactive two EF-hand calcium-binding alder pollen allergen, Aln g 4. Structural basis for calcium-modulated IgE recognition. J. Immunol. 161: 7031-7039.

Vrtala, S., Ball, T., Spitzauer, S., Pandjaitan, B., Suphioglu, C., Knox, B., Sperr, W.R., Valent, P., Kraft, D., and Valenta, R. (1998). Immunization with purified natural and recombinant allergens induces mouse IgG1 antibodies that recognize similar epitopes as human IgE, inhibit the human IgE-allergen interaction and allergen-induced basophil degranulation. J. Immunol. 160: 6137-6144.

Fedorov, A.A., Ball, T.,Mahoney, N.M., R. Valenta, R. and Almo, S. (1997). Crystal structure and IgE-epitope mapping of birch pollen profilin: The molecular basis for allergen cross-reactivity. Structure 5: 33-45.

Laffer, S., Valenta, R., Vrtala, S., Susani, M., vanRee, R., Kraft, D., Scheiner, O. and Duchêne, M. (1994). cDNA cloning of the major allergen Phl p I from timothy grass (Phleum pratense); recombinant Phl p I inhibits IgE-binding to  group I allergens from eight different grass species. J. Allergy Clin. Immunol. 94: 689-698.

Vrtala, S., Sperr, W.R., Reimitzer, I., VanRee, R., Laffer, S., Müller, W.D., Valent, P., Lechner, K., Rumpold, H., Kraft, D., Scheiner, O., and Valenta, R. (1993). cDNA cloning of a major allergen from timothy grass (Phleum pratense) pollen: Characterization of the recombinant Phl p 5 allergen. J. Immunol. 151: 4773-4781.

Ebner, C., Ferreira, F., Szephalusi, Z., Jilek, A., Valenta, R., Parronchi, P., Maggi, E., Romagnani, S., Scheiner, O. and Kraft, D. (1993). Identification of multiple T-cell epitopes on Bet v I, the major birch pollen allergen using specific T cell clones and overlapping peptides. J. Immunol. 150: 1047-1054.

Valenta, R., Duchêne, M., Pettenburger, K., Sillaber, C., Valent, P.,  Bettelheim, P., Breitenbach, M., Rumpold, H., Kraft, D. and Scheiner, O. (1991). Identification of profilin as a novel pollen allergen; IgE autoreactivity in sensitized individuals. Science 253: 557-560.

Breiteneder, H., Pettenburger, K., Bito, A., Valenta, R., Kraft, D., Rumpold, H., Scheiner, O. and Breitenbach, M. (1989). The gene coding for the major birch pollen allergen, Bet v I, is highly homologous to a pea disease resistance response gene. EMBO J. 8: 1935-1938.

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Recombinant Allergens - Diagnostic Use

Wickman, M., Lupinek, C., Andersson, N., Belgrave, D., Asarnoj.A., Benet, M., Pinart, M., Wieser, S., Garcia-Aymerich, J., Baar, A. Pershagen, G., Simpson, A., Kull, I., Bergström, A., Melén, E., Hamsten, C., Antó, J.M., Bousquet, J. Custovic, A., Valenta, R., Van Hage, M. (2017) Detection of IgE reactivity to a handful of allergen molecules in early childhood predicts respiratory allergy in adolescence EBioMedicine 12: 91-99

Curin, M., Garib., V., Valenta R. (2017) Single recombinant and purified Major allergens and Peptides: how they are made and how they change allergy diagnosis and treatment Ann. Allergy Asthma Immunol. 119: 201-209

Saltabayeva, U., Garib., V. Morenko, M., Rosenson, R., Ispayeva, Z., Gatauova, M., Zulus, L., Karaulov, A., Gastager, F., Valenta. R. (2017) Greater real-life diagnostic efficacy of allergen molecule-based diagnosis for prescription of immunotherapy in an area with multiple pollen exposure Int. Arch. Allergy Immunol. 173: 93-98

Asarnoj, A. Hamsten, C., Lupinek, C., Melén, E., Andersson, N., Antó, J.M., Bousquet, J., Valenta, R., van Hage, M., Wickman, M., MeDALL Consortuium (2017) Prediction of peanut allergy in adolescence by early childhood storage Protein IgE signatures: the BAMSE population-based birth cohort, J Allergy Clin. Immunol. 140: 587-590

Berings, M., Arasi, S., de Ruyck, N., Perna, S., Resch, Y., Lupinek, C., Chen, K.W., Vrtala, S., Pajno, G.B., Bachert, C., Lambrecht, B.N., Dullaers, M., Valenta, R., Matricardi, P.M., Gevaert, P. (2017) Reliable mite-specific IgE testig in nasal secretions by means of allergen microarray. J Allergy Clin. immunol. 140: 301-303

Posa, D., Perna, S., Resch, Y., Lupinek, C., Panetta, V., Hofmaier, S., Rohrbach, A., Hatzler, J., Grabenhenrich, L., Tsilochristou, O., Chen K.W., Bauer, C.P., Hoffman, U., Forster, J., Zepp, F., Schuster, A., Wahn, U., Keil, T. Lau, S. Vrtala, S., Vlenta, R., Matricardi, P.M. (2017) Evolution and predictive value of IgE Responses toward a comprehensive panel of house dust mite allergens duirng the first 2 decades of life J. Allergy Clin Immunol. 139: 541-549

Lupinek, C., Wollmann, E., Valenta, R. (2016) Monitoring allergen immunotherapy effects by microarray Curr. Treat. Options Allergy 3:189-203

Wollmann, E., Lupinek, C., Kundi, M., Selb; R., Niederberger, V., Valenta, R. (2015) Reduction in allergen-specific IgE binding as measured by microarray: a possible surrogate marker for effects of specific immunotherapy.  J. Allergy Clin. Immunol. 136::806-809

Lupinek, C., Wollmann., E, Baar, A., Banerjee, S., Breiteneder, H., Broecker, B.M., Bublin, M., Curin, M., Flicker, S., Garmatiuk, T., Hochwallner, H., Mittermann, I., Pahr, S., Resch, Y., Roux, K.H., Srinivasan, B., Stentzel, S., Vrtala, S., Willison, L.N., Wickman, M., Lødrup-Carlsen, K.C., Antó, J.M., Bousquet, J., Bachert, C., Ebner, D., Schlederer, T., Harwanegg, C., Valenta, R. (2014) Advances in allergen-microarray technology for diagnosis and monitoring of allergy: the MeDALL allergen-chip. Methods 66, 106-119

Gadermaier, G., Wopfner, N., Wallner, M., Egger, M., Didierlaurent, A., Regl, G., Aberger, F., Lang, R., Ferreira, F. and Hawranek, T. (2008). Array-based profiling of ragweed and mugwort pollen allergens. Allergy 63(11): 1543-1549.

Stern, D.A., Riedler, J., Nowak, D., Braun-Fahrlander, C., Swoboda, I., Balic, N., Chen, K.W., Vrtala, S., Grönlund, H., van Hage, M., Valenta, R., Spitzauer, S., von Mutius, E. and Vercelli, D. (2007). Exposure to a farming environment has allergen-specific protective effects on Th2-dependent isotype switching in response to common inhalants. J. Allergy Clin. Immunol. 119: 351-358.

Purohit, A., Laffer, S., Metz-Favre, C., Verot, A., Kricek, F., Valenta, R. and Pauli, G. (2005). Poor association between allergen-specific serum IgE levels, skin sensitivity and basophil degranulation : A study with recombinant birch pollen allergen Bet v 1 and an IgE detection system measuring IgE capable of binding to FceRI. Clin. Exp. Allergy 35: 186-192.

Harwanegg, C., Laffer, S., Hiller, R., Müller, M.W., Kraft, D., Spitzauer, S. and Valenta, R. (2003). Microarrayed recombinant allergens for diagnosis of allergy. Clin. Exp. Allergy 33: 7-13.

Niederberger, V., Niggemann, B., Kraft, D., Spitzauer, S. and Valenta, r. (2002). Evolution of IgM, IgE and IgG1-4 antibody responses in early childhood monitored with recombinant allergen components: Implications for class switch mechanisms. Eur. J. Immunol. 32: 576-584.

Niederberger, V., Pauli, G., Grönlund, H., Fröschl, R., Rumpold, H., Kraft, D., Valenta, R. and Spitzauer, S. (1998). Recombinant birch pollen alergens (rBet v 1, rBet v 2) contain most of the IgE epitopes present in birch, alder, hornbeam, hazel and oak pollen. A quantitative IgE inhibition study with sera from different populations. J. Allergy Clin. Immunol. 102: 579-591.

Laffer, S., Spitzauer, S., Susani, M., Pairleitner, P., Schweiger, C., Grönlund, H., Menz, G., Pauli, G., Ishii, T., Nolte, H., Ebner, C., Sehon, A.H., Kraft, D., Eichler, H.G. and Valenta, R. (1996). Comparison of recombinant timothy grass pollen allergens with natural extract for diagnosis of grass pollen allergy in different populations. J. Allergy Clin. Immunol. 98: 652-658.

Valenta R., Sperr, W.R., Ferreira, F., Valent, P., Sillaber, C., Tejkl, M., Duchêne, M., Ebner, C., Lechner, K., Kraft, D. and Scheiner, O. (1993). Induction of allergen-specific histamine release from basophils with purified natural and recombinant birch pollen allergens. J. Allergy Clin. Immunol. 91: 88-97.

Valenta, R., Duchêne, M., Vrtala, S., Birkner, T., Ebner, C., Hirschwehr, R., Breitenbach, M., Rumpold, H., Scheiner, O. and Kraft, D. (1991). Recombinant allergens for immunoblot diagnosis of tree-pollen allergy. J. Allergy Clin. Immunol. 88: 889-894.

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Hypoallergens and Allergen Derivatives

Freidl, R., Gstoettner, A., Baranyi, U., Swoboda, I., Stolz, F., Focke-Tejkl, M., Wekerle, T., van Ree, R., Valenta, R., Linhart, B. (2017) Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy. J. Allergy Clin. Immunol. 139: 1897-1905 

Douladiris, N., Linhart, B, Swoboda, I., Gstöttner, A., Vassilipoulou, E., Stolz, F., Valenta, R. Papadopoulos, N.G. (2015) In vivo allergenic activity of a hypoallergenic mutant of the major fish allergen Cyp c 1 evaluated by means of skin testing J. Allergy Clin, immunol. 136: 493-495

Swoboda, I., Balic, N., Klug, C., Focke, M., Weber, M., Spitzauer, S., Neubauer, A., Quirce, S., Douladiris, N., Papadopoulos, N.G., Valenta, R. (2013) A general strategy for the generation of hypoallergenic molecules for the immunotherapy of fish allergy. J Allergy Clin Immunol. 132:979-81

Pichler, U., Asam, C., Weiss, R. Isakovic, A., Hauser, M., Briza, P., Ferreira, F., Wallner, M. (2013) The fold variant BM4 is beneficial in a therapeutic
Bet v 1 mouse model.
BioMed Res. Itnl.

Chen K.W., Blatt, K., Thomas, W.R., Swoboda, I., Valent, P., Valenta, R., Vrtala, S.  (2012) Hypoallergenic Der p 1/Der p 2 combination vaccines for immunotherapy of house dust mite allergy. J. Allergy Clin. Immunol. 130: 435-443

Zuidmeer-Jongejan, L. Fernandez-Rivas, M, Poulsen, L.K., Neubauer,A. et al. (2012) FAST: towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies. Clin. Transl. Allergy 2:5

Vrtala, S., Fohr, M., Campana, R., Baumgartner, C., Valent, P., Valenta, R. (2011)  Genetic Engineering of trimers of hypoallergenic fragments of the major birch pollen allergen Bet v 1 for allergy vaccination. Vaccine 29: 2140 -2148

Wallner, M., Hauser, M., Himly, M., Zaborsky, N., Mutschlechner, S., Harrer, A., Asam, C., Pichler, U., van Ree, R. Briza, P., Thalhamer, J., Bohle, B., Achatz, G., Ferreira, F. (2011) Reshaping the Bet v 1 fold modulates TH polarization. J. Allergy Clin. Immunol. 127:1571-1578

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

Wopfner, N., Jahn-Schmid, B., Schmidt, G., Christ, T., Hubinger, G., Briza, P., Bohle, B., Vogel, L., Ebner, C., Asero, R., Ferreira, F. and  Schwarzenbacher, R. (2009). The alpha and beta subchain of Amb a 1, the major ragweed pollen allergen show divergent reactivity at the IgE and T cell level. Mol. Immunol. (Accepted for publication).

Linhart, B., Mothes-Luksch, N., Vrtala, S., Kneidinger, M., Valent, P. and Valenta, R. (2008). A hypoallergenic hybrid molecule with increased immunogenicity consisting of derivatives of the major grass pollen allergens, Phl p 2 and Phl p 6. Biol. Chem. 389: 925-933.

Mothes-Luksch, N., Stumvoll, S., Linhart, B., Focke, M., Kraut, M.T., Hauswrith, A., Valent, P., Verdino, P., Pavkov, T., Keller, W., Grote M. and Valenta, R. (2008). Disruption of allergenic activity of the major grass pollen allergen Phl p 2 by reassembly as a mosaic protein. J. Immunol. 181: 4864-4873.

Swoboda, I., Bugajska-Schretter, A., Linhart, B., Verdino, P., Keller, W., Schulmeister, U., Sperr, W.R., Valent, P., Peltre, G., Quirce, S., Douladiris, N., Papadopoulos, N.G., Valenta, R. and Spitzauer, S. (2007). A recombinant hypoallergenic parvalbumin mutant for immunotherapy of IgE mediated fish allergy. J. Immunol. 178: 6290-6296.

Vrtala, S., Focke, M., Kopec, J., Verdino, P., Hartl, A., Sperr, W.R., Fedorov, A.A., Ball, T., Almo, S., Valent, P., Thalhamer, J., Keller, W. and Valenta, R. (2007). Genetic engineering of the major timothy grass pollen allergen, Phl p 6, to reduce allergenic activity and preserve immunogenicity. J. Immunol.  179: 1730-1739.

Wallner, M., Stöcklinger, A., Thalhamer, T., Bohle, B., Vogel, L., Briza, P., Breiteneder, H., Vieths, S., Hartl., A., Mari, A., Ebner, C., Lackner, P., Hammerl., P., Thalhamer, J. and Ferreira, F. (2007). Allergy multi-vaccines created by DNA shuffling of tree pollen allergens. J. Allergy Clin. Immunol. 120: 374-380.

Westritschnig, K., Linhart, B., Focke-Tejkl, M., Pavkov, T., Keller, W., Ball, T., Mari, A., Hartl, A., Stöcklinger, A., Scheiblhofer, S., Thalhamer, J., Ferreira, F., Vieths, S., Böhm, A., Valent, P. and Valenta, R. (2007). A hypoallergenic vaccine obtained by tail-to-head restructuring of timothy grass pollen profilin, Phl p 12, for the treatment of cross-sensitization to Profilin.  J. Immunol. 179: 7624-7634.

Ma, Y., Gadermaier, G., Bohle, B., Bolhaar, S., Knulst, A., Breiteneder, H., Briza, P., Hoffmann-Sommergruner, K. and Ferreira, F. (2006). Amino acid positions involved in the formation of IgE-binding epitopes of Mal d 1, the major apple allergen. Int. Arch. Allergy Immunol. 139: 53-62.

Linhart, B., Hartl, A., Jahn-Schmid, B., Verdino, P., Keller, W., Krauth, M.T., Valent, P., Horak, F., Wiedermann, U., Thalhamer, J., Ebner, C., Kraft, D. and Valenta, R. (2005). A hybrid molecule resembling the epitope spectrum of grass pollen for allergy vaccination. J. Allergy Clin. Immunol. 115: 1010-1016.

Ferreira, F., Wallner, M. and Thalhamer, J. (2004). Costumized antigens and immunomodulations for desensitizing allergic patients. Adv. Immunol. 84: 79-129.

Westritschnig, K., Focke, M., Verdino, P., Goessler, W., Keller, W., Twardosz, A., Mari, A., Horak, F., Wiedermann, U., Hartl, A., Thalhamer, J., Sperr, W.R., Valent, P. and Valenta, R. (2004). Generation of an allergy vaccine by disruption of the three-dimensional structure of the cross-reactive calcium-binding allergen, Phl p 7. J. Immunol., 172: 5684-5692.

Mahler, V., Vrtala, S., Kuss, O., Diepgen, T.L., Suck, R., Cromwell, O., Fiebig, H., Hartl, A., Thalhamer, J., Schuler, G., Kraft, D. and Valenta, R. (2004). Vaccines for birch pollen allergy based on genetically-engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1. Clin. Exp. Allergy 34: 115-122.

B. Linhart, Jahn-Schmid, B., Verdino, P., Keller, W., Ebner, C., Kraft, D., and Valenta, R. (2002). Combination vaccines for the treatment of grass pollen allergy consisting of genetically engineered hybrid molecules with increased immunogenicity. FASEB J. 16. 1301-1303.

Vrtala, S., Hirtenlehner, K., Susani, M., Akdis, M., Kussebi, F., Akdis, C.A., Blaser, K., Hufnagl, P., Binder, B.R., Politou, A., Pastore, A., Vangelista, L., Sperr, W.R., Sempber, H., Valent, P., Ebner, C., Kraft, D. and Valenta, R. (2001). Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen, Bet v 1. FASEB J. 15: 2045-2047. 

Vrtala, S., Akdis, C.A., Budak, F., Akdis, M., Blaser, K., Kraft, D. and Valenta, R. (2000). T cell epitope-containing hypoallergenic recombinant fragments of the major birch pollen allergen, Bet v 1, induce blocking antibodies. J. Immunol. 165: 6653-6659.

Vrtala, S., Hirtenlehner, K., Vangelista, L., Pastore, A., Eichler, H.G., Sperr, W.R., Valent, P., Ebner, C., Kraft, D. and Valenta, R. (1997). Conversion of the major birch pollen allergen, Bet v 1, into two non-anaphylactic T-cell epitope-containing fragments; candidates for a novel form of specific immunotherapy. J. Clin. Invest. 99: 1673-1681.

Ferreira, F., Hirtenlehner, K., Jilek, A., Godnik-Cvar, J., Breiteneder, H., Grimm, R., Hoffmann-Sommergruber, K., Scheiner, O., Kraft, D., Breitenbach, M., Rheinberger, H.J. and Ebner, C. (1996). Dissection of IgE-binding and T lymphocyte reactivity of isoforms of Bet v 1, the major birch pollen allergen: Potential use of hypoallergenic isoforms for immunotherapy. J. Exp. Med. 183: 599-609

Ball, T., Vrtala, S., Sperr, W.R., Valent, P., Susani, M., Kraft, D. and Valenta, R. (1994). Isolation of an immunodominant IgE-hapten from an epitope expression cDNA library; dissection of the allergic effector reaction. J. Biol. Chem. 269: 28323-28328.

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B-cell Epitope Related Peptides

Valenta, R., Campana, R., Niederberger, V., (2017) Recombinant allergy vaccines based on allergen-derived B cell epitopes, Immunology Lett. (in press,

Niederberger, V., Neubauer, A., Gevaert, P., Zidarn, M., Worm, M., Aberer, W., Malling HJ., Pfaar, O., Klimek, L., Pfützner, W., Ring, J., Darsow, U., Novak, N., Gerth van Wijk, R., Eckl-Dorna, J., Focke-Tejkl, M., Weber, M., Müller, H-H., Klinger, J., Stolz, F., Breit, N., Henning, R., Valenta, R.,(2018) Safety and efficacy of immunotherapy with the recombinant B-cell epitope-based grass pollen vaccine BM32, J. Allergy Clin. Immunol. (in press,

Zieglmayer, P., Focke-Tejkl, M., Schmutz, R., Lemell, P., Zieglmayer, R., Weber, M., Kiss, R., Blatt, K., (2016) Mechanism, safety, and efficacy of a B-cell epitope based vaccine for immunotherapy of grass pollen allergy, EBioMedicine 11: 43-57

Weber, M., Niespodziana, K., Linhart, B., Neubauer, A., Huber, H., Henning, R., Valenta, R., Focke-Tejkl, M. (2017) Comparison of the immunogenicity of BM32, a recombinant hypoallergenic B cell-epitope based grass pollen allergy vaccine with allergen extract based vaccines, J. Allergy Clin. Immunol. 140: 1433-1436

Niederberger, V., Marth, K., Eckel-Dorna, J., Focke-Tejkl, M., Weber, M., Hammer, W., Berger, U., Neubauer, A., et al. (2015) Skin test evaluation of a novel peptide-carrier based vaccine, BM32, in grass-pollen allergic patients J Allergy Clin. Immunol. 136: 1101-1103

Focke-Tejkl, M., Weber, M., Niespodzaina, K., Huber, H., Henning, R., Stegfellner, G., Maderegger, B., Hauer, M., Stolz, F., Niederberger, V., Marth, K., Eckl.Dorna, J., Blatt, K., Valent, P., Valenta, R. (2014)Development and characterization of BM32, a hypoallergenic grass pollen vaccine based on peptide-carrier technology. J. Allergy Clin. Immunol. 135:1207-1217

Banerjee, S., Weber, M., Blatt, K., Swoboda, I., Focke-Tejkl, M., Valent, P., Valenta, R., Vrtala, S. (2014) Conversion of Der p 23, a new major house dust mite allergen, into a hypoallergenic vaccine. J. Immunol. 192: 4867-4875

Marth, K., Breyer, I., Focke-Tejkl, M., Blatt, K., Shamji, M.H., Layhadi, J., Gieras, A., Swoboda, I., Zafred, D., Keller, W., Valent, P., Durham, S.R., Valenta, R. A nonallergenic 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. 190:3068-3078

Twaroch, T.E., Focke, M., Fleischmann, K., Balic, N., Lupinek, C., Blatt, K., Ferrara, R., Mari, A., Ebner, C., Valent, P., Spitzauer, S., Swoboda, I., Valenta, R. (2012) Carrier bound Alt a 1 peptides without allergenic activity for vaccination against Alternaria alternata allergy. Clin. Exp. Allergy 42: 966-975

Chen, K.W., Focke-Tejkl, M., Blatt, K., Kneidinger, M., Gieras, A., Dall'Antonia, F., Faé, I., Fischer, G., Keller, W., Valent, P., Valenta, R., Vrtala, S.(2012) Carrier bound nonallergenic Der p 2 peptides induce IgG antibodies blocking allergen-induced basophil activation in allergic patients. Allergy 67:609-621

Twaroch, T.E., Focke, M., Civaj, V., Weber, M., Balic, N., Mari, A., Ferrara, R., Quirce, S., Spitzauer, S., Swoboda, I., Valenta, R. Carrier-bound, non-allergenic Ole e 1 peptides for vaccination against olive pollen allergy. J. Allergy Clin. Immunol. 352: 121-140

Niespodziana K., Focke-Tejkl, M., Linhart, B., Civaj, V., Blatt, K., Valent, P., van Hage, M., Grönlund, H., Valenta, R. A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to Hepatitis B PreS. J. Allergy Clin. Immunol. 127: 1562-1570


Tinhofer, J., Niespodziana, K., Linhart, B., Focke-Tejkl, M., Westritschnig, K., Scheiblhofer, S., Stoecklinger, A., Kneidinger, M., Valent, P., Campana, R., Thalhamer, J., Popow-Kraupp, T. and Valenta, R. (2009). A combination vaccine for allergy and rhinovirus infections based on rhinovirus-derived surface protein VP1 and a non-allergenic peptide of the major timothy grass pollen allergen, Phl p 1. J Immunol 182:6298-306.

Focke, M., Linhart, B., Hartl, A., Wiedermann, U., Sperr, W.R., Valent, P., Thalhamer, J., Kraft, and D., Valenta, R. (2004). Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination. Clin. Exp. Allergy 34(10): 1525-1533.

Focke, M., Mahler, V., Ball, T., Sperr, W.R., Majlesi, Y., Valent, P., Kraft, D. and Valenta, R. (2001). Nonanaphylactic synthetic peptides derived from B cell epitopes of the major grass pollen allergen, Phl p 1, for allergy vaccination. FASEB J. 15(11):2042-2044.

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T-cell Based Approaches to Specific Immunotherapy

Bohle, B. (2008). T cell responses during allergen-specific immunotherapy of Type I allergy. Front Biosci. 13: 6079- 6085. 

Jahn-Schmid, B., Sirven, P., Leb, V., Pickl, W.F., Fischer, G.F., Gadermaier, G., Egger, M., Ebner, C., Ferreira, F., Maillére B. and Bohle, B. (2008). Characterization of HLA-class II / peptide-TCR interactions of the immunodominant T cell epitope in Art v 1, the major mugwort pollen allergen. J. Immunol. 181: 3636-3642. 

Leb, V.M., Jahn-Schmid, B.,  Schmetterer, K.G.,  Kueng, H. J., Haiderer, D.,  Neunkirchner, A., Fischer, G.F., Nissler, K.,  Hartl, A., Thalhamer, J., Bohle, B., Seed, B. and Pickl W.F. (2008). Molecular and functional analysis of the antigen receptor of Art v 1-specific helper T lymphocytes. J. Allergy Clin. Immunol. 121: 64-71. 

Van Overtvelt, L.,  Wambre, E., Maillère, B., von Hofe, E., Louise, A., Balazuc, A.M., Bohle, B., Ebo, D., Leboulaire, C., Garcia, G. and Moingeon P. (2008). Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers. J. Immunol. 180: 4514-4522. 

Bohle, B. (2006). T-cell epitopes of food allergens. Clinical Reviews in Allergy & Immunology 30: 97-108.

Jahn-Schmid, B., Radakovics, A.,  Lüttkopf, D., Scheurer, S., Vieths, S., Ebner, C. and Bohle, B. (2005). Bet v 1142-156 is the dominant T cell epitope of the major birch pollen allergen and important for cross-reactivity with Bet v 1-related food allergens. J. Allergy Clin. Immunol. 116: 213-219.

Jahn-Schmid, B., Fischer, G.F., Bohle, B., Faé, Gadermaier, G., Dedic, A., Ferreira, F. and Ebner, C.  (2005). Antigen-presentation of the immunodominant T cell epitope of the major mugwort pollen allergen, Art v 1, is associated with the expression of HLA-DRB1*01. J. Allergy Clin. Immunol. 115: 399-404.

Bohle, B., Radakovics, A., Jahn-Schmid, B.,  Hoffmann-Sommergruber, K., Fischer, G.F. and Ebner, C. (2003). Bet v 1, the major birch pollen allergen, initiates sensitization to Api g 1, the major allergen in celery: evidence at the T cell level. Eur. J. Immunol. 33: 3303-3310. 

Jahn-Schmid, B., Kelemen, P., Himly, M., Bohle, B., Fischer, G., Ferreira, F. and Ebner, C. (2002). The T cell response to Art v 1, the major mugwort pollen allergen, is dominated by one epitope. J. Immunol. 169: 6005-6011.

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Genetic Allergy Vaccines

Scheiblhofer, S., Stoecklinger, A., Gruber, C., Hauser-Kronberger, C., Alinger, B., Hammerl, P., Thalhamer, J. and Weiss, R. (2007). Gene gun immunization with clinically relevant allergens aggravates allergen induced pathology and is contraindicated for allergen immunotherapy. Mol. Immunol. 44: 1889-1897.

Wallner, M., Stöcklinger, A., Thalhamer, T., Bohle, B., Vogel. L., Briza, P., Breiteneder, H., Vieths, S., Hartl, A., Mari, A., Ebner, C., Lackner, P., Hammerl, P., Thalhamer, J. and Ferreira, F. (2007). Allergy multi-vaccines created by DNA shuffling of tree pollen allergens. J. Allergy Clin. Immunol. 120: 374-380.

Bauer, R., Scheiblhofer, S., Kern, K., Gruber, C., Stepanoska, T., Thalhamer, T., Hauser-Kronberger, C., Alinger, B., Zögg, T., Gabler, M., Ferreira, F., Hartl, A., Thalhamer, J. and Weiss, R. (2006). Generation of hypoallergenic DNA vaccines by forced ubiquitination: Preventive and therapeutic effects in a mouse model of allergy. J. Allergy Clin. Immunol. 118: 269-276.

Gabler, M., Scheiblhofer, S., Kern, K., Leitner, W.W., Hauser-Kronberger, C, Alinger, Beate., Valenta, R., Thalhamer, J. and Weiss, R. (2006). Immunization with nanogram doses of a replicon DNA vaccine encoding Phl p 5 effectively prevents from allergic reactions. J. Allergy Clin. Immunol. 118: 734-741.

Scheiblhofer, S., Gabler, M., Leitner, W.W., Bauer, R., Zögg, T., Ferreira, F., Thalhamer, J. and Weiss, R. (2006). Effective inhibition of type I allergic responses with nanogram doses of replicon-based DNA vaccines. Allergy 118: 269-276. 

Scheiblhofer, S., Weiss, R., Leitner , W.W. and Thalhamer, J. (2006). Replicase-based DNA vaccines for allergy treatment. Methods Mol. Med. 127: 221-236.

Weiss, R., Scheiblhofer, S., Gabler, M., Ferreira, F., Leitner, W.W. and Thalhamer, J. (2006). Is genetic vaccination against allergy possible? Int. Arch. Allergy Immunol. 139: 332-345. 

Weiss, R., Scheiblhofer, S. and Thalhamer, J. (2006). DNA vaccines for allergy treatment. Methods Mol. Med. 127: 253-268.

Weiss, R., Hammerl, P., Hartl, A., Hochreiter, R., Leitner, W.W., Scheiblhofer, S. and Thalhamer, J. (2005). Design of protective and therapeutic DNA vaccines for the treatment of allergic diseases. Curr. Drug Targets Inflamm. Allergy 4: 585-597.

Hartl, A., Hochreiter, R., Stepanoska, T., Ferreira, F. and Thalhamer J. (2004). Characterization of the protective and therapeutic efficiency of a DNA vaccine encoding the major birch pollen allergen Bet v 1a. Allergy 59: 65-73.

Bauer, R., Himly, M., Dedic, A., Ferreira, F., Thalhamer, J. and Hartl, A. (2003). Optimization of Codon Usage is required for effective genetic immunization against Art v 1, the major allergen of mugwort pollen. Allergy 58: 1003-1010. 

Leitner, W. and Thalhamer, J. (2003). DNA vaccines for non-infectious disease. Expert Opin. Biol. Ther. 3: 627-638.

Hartl A., Kiesslich J., Weiss R., Bernhaupt A., Mostböck S., Scheiblhofer S., Ebner C., Ferreira F. and Thalhamer J. (1999). Immune responses after immunization with plasmid DNA encoding Bet v 1, the major allergen of birch pollen. J. Allergy Clin. Immunology 103: 107-113.

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Cell Based Approach to Tolerance Induction

Baranyi, U., Linhart, B., Pilat, N., Bagley, J., Muehlbacher, F., Iacomini, J., Valenta, R. and Wekerle, T. (2008).  Tolerization of a type I allergic immune response through transplantation of genetically modified hematopoietic stem cells. J. Immunol. 180(12):  8168-8175.

Wekerle, T. and Sykes, M. (2001). Mixed chimerism and transplantation tolerance. Annu Rev Med. 52: 353-370.

Wekerle,T., Kurtz, J., Ito, H., Ronquillo, J.V., Dong, V., Zhao, G., Shaffer, J., Sayegh, M.H. and Sykes, M. (2000). Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment. Nature Medicine 6(4) 464-469.

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Antibody Based Approaches to Allergy Therapy

Madritsch, C., Eckl-Dorna, J., Blatt, K., Ellinger, I., Kundi, M., Niederberger, V., Valent, P. Valenta, R., Flicker, S. (2015) Antibody conjugates bispecific for intercellular adhesion molecule 1 and allergen prevent migration of allergens through respiratory epithelial cell layers. J. Allergy Clin. immunol. 136:490-493

Flicker, S., Linhart, B., Wild, C., Wiedermann, U., Valenta, R. (2013) Passive immunization with allergen-specific IgG antibodies for treatment and prevention of allergy. Immunobiology 218:884-91

Laffer, S., Lupinek, C., Rauter, I., Kneidinger, M., Drescher, A., Jordan, J.H., Krauth, M.T., Valent, P., Kricek, F., Spitzauer, S., Englund, H. and Valenta, R. (2008).  A high-affinity monoclonal anti-IgE antibody for depletion of IgE and IgE-bearing cells. Allergy 63(6): 695-702.

Flicker, S., Steinberger, P., Norderhaug, L., Sperr, W.R., Majlesi, Y., Valent, P., Kraft, D. and Valenta, R. (2002). Conversion of grass pollen allergen-specific human IgE into a protective IgG1 antibody. Eur. J. Immunol. 32: 2156–2162.

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Adjuvants for Allergy Immunotherapy

Gerstmayr, M., Ilk, N., Schabussova, I., Jahn-Schmid, B., Egelseer, E.M., Sleytr, U.B., Ebner, C. and Bohle, B. (2007). A Novel Approach to Specific Allergy Treatment: The Recombinant Allergen-S-Layer Fusion Protein rSbsC-Bet v 1 Matures Dendritic Cells that Prime Th0/Th1 and IL-10-Producing Regulatory T Cells. J. Immunol. 179: 7270-7275.

Bohle, B., Breitwieser, A., Zwölfer, B., Jahn-Schmid, B., Sára, M., Sleytr, U.B.  and Ebner, C. (2004). A Novel Approach to Specific Allergy Treatment: The recombinant fusion protein of a bacterial cell surface (S-layer) protein and the major birch pollen allergen Bet v 1 (rSbsC-Bet v1) combines reduced allergenicity with immunomodulating capacity. J. Immunol. 172(11): 6642-6648.

Grönlund, H., Vrtala, S., Wiedermann, U., Dekan, G., Kraft, D., Valenta, R., and van Hage-Hamsten, M. (2002). Carbohydrate-based articles: a new adjuvant for allergen-specific immunotherapy. Immunology 107:523-529.

Bohle, B., Orel, L., Kraft, D. and Ebner, C. (2001). Oligodeoxynucleotides containing CpG motifs induce low levels of TNF-alpha in human B lymphocytes: possible adjuvants for Th1 responses. J. Immunol. 166: 3743-3748.

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