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2. Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products

Author

Bonertz, A., Roberts, G. C., Hoefnagel, M., Timon, M., Slater, J. E., Rabin, R. L., Bridgewater, J., Pini, C., Pfaar, O., Akdis, C., Goldstein, J., Poulsen, L. K., van Ree, R., Rhyner, C., Barber, D., Palomares, O., Sheikh, A., Pawankar, R., Hamerlijnk, D., Klimek, L., Agache, I., Angier, E., Casale, T., Fernandez‐Rivas, M., Halken, S., Jutel, M., Lau, S., Pajno, G., Sturm, G., Varga, E. M., Gerth van Wijk, R., Bonini, S., Muraro, A., and Vieths, S.

Published
2018
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6. Global Allergy Forum and 3rd Davos Declaration 2015: Atopic dermatitis/Eczema: challenges and opportunities toward precision medicine

Author

Bieber, T., Akdis, C., Lauener, R., Traidl-Hoffmann, C., Schmid-Grendelmeier, P., Schäppi, G., Allam, J.-P., Apfelbacher, C., Augustin, M., Beck, L., Biedermann, T., Braun-Fahrländer, C., Chew, F. T., Clavel, T., Crameri, R., Darsow, U., Deleuran, M., Dittlein, D., Duchna, H.-W., Eichenfeld, L., Eyerich, K., Frei, R., Gelmetti, C., Gieler, U., Gilles, S., Glatz, M., Grando, K., Green, J., Gutermuth, J., Guttman-Yassky, E., Hanifin, J., Hijnen, D., Hoetzenecker, W., Irvine, A., Kalweit, A., Katoh, N., Knol, E., Koren, H., Möhrenschlager, M., Münch, D., Novak, N., OʼMahony, L., Paller, A. S., Rhyner, C., Roduit, C., Schiesser, K., Schröder, J., Simon, D., Simon, H.-U., Sokolowska, M., Spuls, P., Stalder, J.-F., Straub, D., Szalai, Z., Taieb, A., Takaoka, R., Todd, G., Todorova, A., Vestergaard, C., Werfel, T., Wollenberg, A., and Ring, J.

Published
2016
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12. Global Allergy Forum and Second Davos Declaration 2013 Allergy: Barriers to cure – challenges and actions to be taken

Author

Ring, J., Akdis, C., Lauener, R., Schäppi, G., Traidl-Hoffmann, C., Akdis, M., Ammann, W., Behrendt, H., Bieber, T., Biedermann, T., Bienenstock, J., Blaser, K., Braun-Fahrländer, C., Brockow, K., Buters, J., Crameri, R., Darsow, U., Denburg, J. A., Eyerich, K., Frei, R., Galli, S. J., Gutermuth, J., Holt, P., Koren, H., Leung, D., Müller, U., Muraro, A., Ollert, M., OʼMahony, L., Pawankar, R., Platts-Mills, T., Rhyner, C., Rosenwasser, L. J., Schmid-Grendelmeier, P., Schmidt-Weber, C. B., Schmutz, W., Simon, D., Simon, H. U., Sofiev, M., van Hage, M., and van Ree, R.

Published
2014
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21. State‐of‐the‐art in marketed adjuvants and formulations in Allergen Immunotherapy: a position paper of the European Academy of Allergy and Clinical Immunology (EAACI)

Author

Jensen‐Jarolim, E; https://orcid.org/0000-0003-4019-5765, Bachmann, M F; https://orcid.org/0000-0003-4370-2099, Bonini, S, Jacobsen, L, Jutel, M; https://orcid.org/0000-0002-6974-5700, Klimek, L, Mahler, V; https://orcid.org/0000-0001-6471-1811, Mösges, R; https://orcid.org/0000-0002-1928-810X, Moingeon, P, O'Hehir, R E; https://orcid.org/0000-0002-3489-7595, Palomares, O; https://orcid.org/0000-0003-4516-0369, Pfaar, O; https://orcid.org/0000-0003-4374-9639, Renz, H; https://orcid.org/0000-0003-0602-7215, Rhyner, C; https://orcid.org/0000-0003-3339-3923, Roth‐Walter, F; https://orcid.org/0000-0001-5005-9228, Rudenko, M; https://orcid.org/0000-0002-6065-9451, Savolainen, J; https://orcid.org/0000-0002-2161-7443, Schmidt‐Weber, C B; https://orcid.org/0000-0002-3203-8084, Traidl-Hoffmann, Claudia; https://orcid.org/0000-0001-5085-5179, Kündig, T; https://orcid.org/0000-0003-3863-8766, Jensen‐Jarolim, E; https://orcid.org/0000-0003-4019-5765, Bachmann, M F; https://orcid.org/0000-0003-4370-2099, Bonini, S, Jacobsen, L, Jutel, M; https://orcid.org/0000-0002-6974-5700, Klimek, L, Mahler, V; https://orcid.org/0000-0001-6471-1811, Mösges, R; https://orcid.org/0000-0002-1928-810X, Moingeon, P, O'Hehir, R E; https://orcid.org/0000-0002-3489-7595, Palomares, O; https://orcid.org/0000-0003-4516-0369, Pfaar, O; https://orcid.org/0000-0003-4374-9639, Renz, H; https://orcid.org/0000-0003-0602-7215, Rhyner, C; https://orcid.org/0000-0003-3339-3923, Roth‐Walter, F; https://orcid.org/0000-0001-5005-9228, Rudenko, M; https://orcid.org/0000-0002-6065-9451, Savolainen, J; https://orcid.org/0000-0002-2161-7443, Schmidt‐Weber, C B; https://orcid.org/0000-0002-3203-8084, Traidl-Hoffmann, Claudia; https://orcid.org/0000-0001-5085-5179, and Kündig, T; https://orcid.org/0000-0003-3863-8766

Abstract

Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH)3) is the most frequently used adjuvant, with microcrystalline tyrosine (MCT), monophosphoryl lipid A (MPLA) and calcium phosphate (CaP) used less frequently. Recent studies on humans, and using mouse models, have characterized in part the mechanisms of action of adjuvants on pre‐existing immune responses. AIT differs from prophylactic vaccines that provoke immunity to infectious agents, as in allergy the patient is pre‐sensitized to the allergen. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Contrasting immune effects are seen with different adjuvants. Aluminium hydroxide initially boosts Th2 responses, while the other adjuvants utilised in AIT redirect the Th2 immune response toward Th1 immunity. After varying lengths of time, each of the adjuvants supports tolerance. Further studies of the mechanisms of action of adjuvants may advise shorter treatment periods than the current three‐to‐five‐year regimens, enhancing patient adherence. Improved lead compounds from the adjuvant pipeline are under development and are explored for their capacity to fill this unmet need.

Published
2019

23. Molecular allergen profiling in horses by microarray reveals Fag e 2 from buckwheat as a frequent sensitizer

Author

Einhorn, L; https://orcid.org/0000-0002-5488-5022, Hofstetter, G; https://orcid.org/0000-0003-2077-4479, Brandt, S; https://orcid.org/0000-0002-3837-3422, Hainisch, E K; https://orcid.org/0000-0001-7969-8445, Fukuda, I, Kusano, K; https://orcid.org/0000-0003-3722-9135, Scheynius, A; https://orcid.org/0000-0001-5520-990X, Mittermann, I; https://orcid.org/0000-0002-6240-6730, Resch-Marat, Y; https://orcid.org/0000-0002-7933-2547, Vrtala, S; https://orcid.org/0000-0003-4250-8243, Valenta, R; https://orcid.org/0000-0001-5944-3365, Marti, E; https://orcid.org/0000-0003-1284-4350, Rhyner, C; https://orcid.org/0000-0003-3339-3923, Crameri, R, Satoh, R; https://orcid.org/0000-0002-0139-1766, Teshima, R; https://orcid.org/0000-0003-4310-6430, Tanaka, A; https://orcid.org/0000-0002-7906-5047, Sato, H, Matsuda, H; https://orcid.org/0000-0003-3189-6842, Pali‐Schöll, Isabella; https://orcid.org/0000-0003-2089-6011, Jensen-Jarolim, E; https://orcid.org/0000-0003-4019-5765, Einhorn, L; https://orcid.org/0000-0002-5488-5022, Hofstetter, G; https://orcid.org/0000-0003-2077-4479, Brandt, S; https://orcid.org/0000-0002-3837-3422, Hainisch, E K; https://orcid.org/0000-0001-7969-8445, Fukuda, I, Kusano, K; https://orcid.org/0000-0003-3722-9135, Scheynius, A; https://orcid.org/0000-0001-5520-990X, Mittermann, I; https://orcid.org/0000-0002-6240-6730, Resch-Marat, Y; https://orcid.org/0000-0002-7933-2547, Vrtala, S; https://orcid.org/0000-0003-4250-8243, Valenta, R; https://orcid.org/0000-0001-5944-3365, Marti, E; https://orcid.org/0000-0003-1284-4350, Rhyner, C; https://orcid.org/0000-0003-3339-3923, Crameri, R, Satoh, R; https://orcid.org/0000-0002-0139-1766, Teshima, R; https://orcid.org/0000-0003-4310-6430, Tanaka, A; https://orcid.org/0000-0002-7906-5047, Sato, H, Matsuda, H; https://orcid.org/0000-0003-3189-6842, Pali‐Schöll, Isabella; https://orcid.org/0000-0003-2089-6011, and Jensen-Jarolim, E; https://orcid.org/0000-0003-4019-5765

Abstract

Background Companion animals are also affected by IgE‐mediated allergies, but the eliciting molecules are largely unknown. We aimed at refining an allergen microarray to explore sensitization in horses and compare it to the human IgE reactivity profiles. Methods Custom‐designed allergen microarray was produced on the basis of the ImmunoCAP ISAC technology containing 131 allergens. Sera from 51 horses derived from Europe or Japan were tested for specific IgE reactivity. The included horse patients were diagnosed for eczema due to insect bite hypersensitivity, chronic coughing, recurrent airway obstruction and urticaria or were clinically asymptomatic. Results Horses showed individual IgE‐binding patterns irrespective of their health status, indicating sensitization. In contrast to European and Japanese human sensitization patterns, frequently recognized allergens were Aln g 1 from alder and Cyn d 1 from Bermuda grass, likely due to specific respiratory exposure around paddocks and near the ground. The most prevalent allergen for 72.5% of the tested horses (37/51) was the 2S‐albumin Fag e 2 from buckwheat, which recently gained importance not only in human but also in horse diet. Conclusion In line with the One Health concept, covering human health, animal health and environmental health, allergen microarrays provide novel information on the allergen sensitization patterns of the companion animals around us, which may form a basis for allergen‐specific preventive and therapeutic concepts.

Published
2018

24. Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States:An analysis from the EAACI AIT Guidelines Project

Author

Bonertz, A, Roberts, G, Slater, J E, Bridgewater, J, Rabin, R L, Hoefnagel, M, Timon, M, Pini, C, Pfaar, O, Sheikh, A, Ryan, D, Akdis, C, Goldstein, J, Poulsen, L K, van Ree, R, Rhyner, C, Barber, D, Palomares, O, Pawankar, R, Hamerlijnk, D, Klimek, L, Agache, I, Angier, E, Casale, T, Fernandez-Rivas, M, Halken, S, Jutel, M, Pajno, G, Sturm, G, Varga, E M, Gerth van Wijk, R, Bonini, S, Muraro, A, Vieths, S, Bonertz, A, Roberts, G, Slater, J E, Bridgewater, J, Rabin, R L, Hoefnagel, M, Timon, M, Pini, C, Pfaar, O, Sheikh, A, Ryan, D, Akdis, C, Goldstein, J, Poulsen, L K, van Ree, R, Rhyner, C, Barber, D, Palomares, O, Pawankar, R, Hamerlijnk, D, Klimek, L, Agache, I, Angier, E, Casale, T, Fernandez-Rivas, M, Halken, S, Jutel, M, Pajno, G, Sturm, G, Varga, E M, Gerth van Wijk, R, Bonini, S, Muraro, A, and Vieths, S

Abstract

Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.

Published
2018

25. Challenges in the implementation of EAACI guidelines on allergen immunotherapy:A global perspective on the regulation of allergen products

Author

Bonertz, A, Roberts, G C, Hoefnagel, M, Timon, M, Slater, J E, Rabin, R L, Bridgewater, J, Pini, C, Pfaar, O, Akdis, C, Goldstein, J, Poulsen, L K, van Ree, R, Rhyner, C, Barber, D, Palomares, O, Sheikh, A, Pawankar, R, Hamerlijnk, D, Klimek, L, Agache, I, Angier, E, Casale, T, Fernandez-Rivas, M, Halken, S, Jutel, M, Lau, S, Pajno, G, Sturm, G, Varga, E M, Gerth van Wijk, R, Bonini, S, Muraro, A, Vieths, S, Bonertz, A, Roberts, G C, Hoefnagel, M, Timon, M, Slater, J E, Rabin, R L, Bridgewater, J, Pini, C, Pfaar, O, Akdis, C, Goldstein, J, Poulsen, L K, van Ree, R, Rhyner, C, Barber, D, Palomares, O, Sheikh, A, Pawankar, R, Hamerlijnk, D, Klimek, L, Agache, I, Angier, E, Casale, T, Fernandez-Rivas, M, Halken, S, Jutel, M, Lau, S, Pajno, G, Sturm, G, Varga, E M, Gerth van Wijk, R, Bonini, S, Muraro, A, and Vieths, S

Abstract

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

Published
2018

27. Molecular allergen profiling in horses by microarray reveals Fag e 2 from buckwheat as a frequent sensitizer

Author

Einhorn, L., primary, Hofstetter, G., additional, Brandt, S., additional, Hainisch, E. K., additional, Fukuda, I., additional, Kusano, K., additional, Scheynius, A., additional, Mittermann, I., additional, Resch-Marat, Y., additional, Vrtala, S., additional, Valenta, R., additional, Marti, E., additional, Rhyner, C., additional, Crameri, R., additional, Satoh, R., additional, Teshima, R., additional, Tanaka, A., additional, Sato, H., additional, Matsuda, H., additional, Pali-Schöll, I., additional, and Jensen-Jarolim, E., additional

Published
2018
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28. Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: An analysis from the EAACI AIT Guidelines Project

Author

Bonertz, A., primary, Roberts, G., additional, Slater, J. E., additional, Bridgewater, J., additional, Rabin, R. L., additional, Hoefnagel, M., additional, Timon, M., additional, Pini, C., additional, Pfaar, O., additional, Sheikh, A., additional, Ryan, D., additional, Akdis, C., additional, Goldstein, J., additional, Poulsen, L. K., additional, van Ree, R., additional, Rhyner, C., additional, Barber, D., additional, Palomares, O., additional, Pawankar, R., additional, Hamerlijnk, D., additional, Klimek, L., additional, Agache, I., additional, Angier, E., additional, Casale, T., additional, Fernandez‐Rivas, M., additional, Halken, S., additional, Jutel, M., additional, Lau, S., additional, Pajno, G., additional, Sturm, G., additional, Varga, E. M., additional, Gerth van Wijk, R., additional, Bonini, S., additional, Muraro, A., additional, and Vieths, S., additional

Published
2018
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29. Allergen-loaded strontium-doped hydroxyapatite spheres improve allergen-specific immunotherapy in mice

Author

Garbani, M., Xia, Wei, Rhyner, C., Prati, M., Scheynius, Annika, Malissen, B., Engqvist, Håkan, Maurer, M., Crameri, Reto, Terhorst-Molawi, Dorothea, Garbani, M., Xia, Wei, Rhyner, C., Prati, M., Scheynius, Annika, Malissen, B., Engqvist, Håkan, Maurer, M., Crameri, Reto, and Terhorst-Molawi, Dorothea

Abstract

Background Immunomodulatory interventions play a key role in the treatment of infections and cancer as well as allergic diseases. Adjuvants such as micro- and nanoparticles are often added to immunomodulatory therapies to enhance the triggered immune response. Here, we report the immunological assessment of novel and economically manufactured microparticle adjuvants, namely strontium-doped hydroxyapatite porous spheres (SHAS), which we suggest for the use as adjuvant and carrier in allergen-specific immunotherapy (ASIT). Methods and Results Scanning electron microscopy revealed that the synthesis procedure developed for the production of SHAS results in a highly homogeneous population of spheres. SHAS bound and released proteins such as ovalbumin (OVA) or the major cat allergen Fel d 1. SHAS-OVA were taken up by human monocyte-derived dendritic cells (mdDCs) and murine DCs and did not have any necrotic or apoptotic effects even at high densities. In a murine model of ASIT for allergic asthmatic inflammation we found that OVA released from subcutaneously injected SHAS-OVA led to a sustained stimulation of both CD4+ and CD8+ T-cells. ASIT with SHAS-OVA as compared to soluble OVA resulted in similar humoral responses but in a higher efficacy as assessed by symptom scoring. Conclusion We conclude that SHAS may constitute a suitable carrier and adjuvant for ASIT with great potential due to its unique protein-binding properties.

Published
2017
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30. Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products

Author

Bonertz, A. (A.), Roberts, G., Hoefnagel, M. (M.), Timon, M. (M.), Slater, J.E. (J. E.), Rabin, R.L. (R. L.), Bridgewater, J. (J.), Pini, C. (C.), Pfaar, O. (Oliver), Akdis, C.A., Goldstein, J. (J.), Poulsen, L.K., Van Ree, R., Rhyner, C. (Claudio), Barber, D. (D.), Palomares, O. (O.), Sheikh, A. (Aziz), Pawankar, R. (Ruby), Hamerlijnk, D. (D.), Klimek, L. (Ludger), Agache, I., Angier, E. (E.), Casale, T.B. (Thomas), Fernandez Rivas, M. (M.), Halken, S. (Susanne), Jutel, M. (M.), Lau, S. (Susanne), Pajno, G. (G.), Sturm, G.J., Varga, E.M., Gerth van Wijk, R. (R.), Bonini, S. (Sergio), Muraro, A. (A.), Vieths, S. (S.), Bonertz, A. (A.), Roberts, G., Hoefnagel, M. (M.), Timon, M. (M.), Slater, J.E. (J. E.), Rabin, R.L. (R. L.), Bridgewater, J. (J.), Pini, C. (C.), Pfaar, O. (Oliver), Akdis, C.A., Goldstein, J. (J.), Poulsen, L.K., Van Ree, R., Rhyner, C. (Claudio), Barber, D. (D.), Palomares, O. (O.), Sheikh, A. (Aziz), Pawankar, R. (Ruby), Hamerlijnk, D. (D.), Klimek, L. (Ludger), Agache, I., Angier, E. (E.), Casale, T.B. (Thomas), Fernandez Rivas, M. (M.), Halken, S. (Susanne), Jutel, M. (M.), Lau, S. (Susanne), Pajno, G. (G.), Sturm, G.J., Varga, E.M., Gerth van Wijk, R. (R.), Bonini, S. (Sergio), Muraro, A. (A.), and Vieths, S. (S.)

Abstract

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological

Published
2017
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31. Allergen-loaded strontium-doped hydroxyapatite spheres improve allergen-specific immunotherapy in mice

Author

Garbani, M, Xia, W, Rhyner, C, Prati, M, Scheynius, A, Malissen, B, Engqvist, H, Maurer, M, Crameri, R, Terhorst, D, Garbani, M, Xia, W, Rhyner, C, Prati, M, Scheynius, A, Malissen, B, Engqvist, H, Maurer, M, Crameri, R, and Terhorst, D

Abstract

Background Immunomodulatory interventions play a key role in the treatment of infections and cancer as well as allergic diseases. Adjuvants such as micro- and nanoparticles are often added to immunomodulatory therapies to enhance the triggered immune response. Here, we report the immunological assessment of novel and economically manufactured microparticle adjuvants, namely strontium-doped hydroxyapatite porous spheres (SHAS), which we suggest for the use as adjuvant and carrier in allergen-specific immunotherapy (ASIT). Methods and Results Scanning electron microscopy revealed that the synthesis procedure developed for the production of SHAS results in a highly homogeneous population of spheres. SHAS bound and released proteins such as ovalbumin (OVA) or the major cat allergen Fel d 1. SHAS-OVA were taken up by human monocyte-derived dendritic cells (mdDCs) and murine DCs and did not have any necrotic or apoptotic effects even at high densities. In a murine model of ASIT for allergic asthmatic inflammation we found that OVA released from subcutaneously injected SHAS-OVA led to a sustained stimulation of both CD4+ and CD8+ T-cells. ASIT with SHAS-OVA as compared to soluble OVA resulted in similar humoral responses but in a higher efficacy as assessed by symptom scoring. Conclusion We conclude that SHAS may constitute a suitable carrier and adjuvant for ASIT with great potential due to its unique protein-binding properties.

Published
2017

32. A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A. Vet Immunol Immunopathol

Author

Schüpbach, Gertraud, Torsteindottir, S, Marti, E, Svansson, V, Stefansdottir, SB, Rhyner, C, and Jonsdottir, S

Subjects
630 Agriculture, chemical and pharmacologic phenomena, complex mixtures
Abstract

Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused by bites of Culicoides insects, not indigenous to Iceland. Horses born in Iceland and exported to Culicoides-rich areas are frequently affected with IBH. The aims of the study were to compare immunization with recombinant allergens using the adjuvant aluminum hydroxide (Alum) alone or combined with monophosphoryl lipid A (MPLA) for development of a preventive immunization against IBH. Twelve healthy Icelandic horses were vaccinated intralymphatically three times with 10 μg each of four recombinant Culicoides nubeculosus allergens in Alum or in Alum/MPLA. Injection with allergens in both Alum and Alum/MPLA resulted in significant increase in specific IgG subclasses and IgA against all r-allergens with no significant differences between the adjuvant groups. The induced antibodies from both groups could block binding of allergen specific IgE from IBH affected horses to a similar extent. No IgE-mediated reactions were induced. Allergen-stimulated PBMC from Alum/MPLA horses but not from Alum only horses produced significantly more IFNγ and IL-10 than PBMC from non-vaccinated control horses. In conclusion, intralymphatic administration of small amounts of pure allergens in Alum/MPLA induces high IgG antibody levels and Th1/Treg immune response and is a promising approach for immunoprophylaxis and immunotherapy against IBH.

Published
2016
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33. Novel microparticles create a slow releasing depot for long-term immunostimulation in allergen-specific immunotherapy

Author

Garbani, M., Xia, W., Rhyner, C., Prati, M., Scheynius, A., Bernard Malissen, Engqvist, H., Maurer, M., Crameri, R., Terhorst, D., VAFFIDES, Chantal, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

43rd Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung-e-V (ADF), Vienna, AUSTRIA, MAR 10-12, 2016; International audience; no abstract

Published
2016

34. Allergens in veterinary medicine

Author

Mueller, R S, Janda, J, Jensen-Jarolim, E, Rhyner, C, Marti, E, University of Zurich, and Mueller, R S

Subjects
2403 Immunology, 10183 Swiss Institute of Allergy and Asthma Research, immune system diseases, 2723 Immunology and Allergy, otorhinolaryngologic diseases, 610 Medicine & health, respiratory system, respiratory tract diseases
Abstract

Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in dogs and horses, respectively. In those species, some major allergens differ from those in humans. This position paper summarizes the current knowledge about relevant allergens in dogs, cats and horses.

Published
2016
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35. Interleukins, from 1 to 37, and interferon-gamma: Receptors, functions, and roles in diseases

Author

Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H, Gomez E, Klunker S, Meyer N, O'Mahony L, Palomares O, Rhyner C, Quaked N, Schaffartzik A, Van De Veen W, Zeller S, Zimmermann M, and Akdis CA

Abstract

Advancing our understanding of mechanisms of immune regulation in allergy asthma autoimmune diseases tumor development organ transplantation and chronic infections could lead to effective and targeted therapies. Subsets of immune and inflammatory cells interact via ILs and IFNs; reciprocal regulation and counter balance among T H and regulatory T cells as well as subsets of B cells offer opportunities for immune interventions. Here we review current knowledge about ILs 1 to 37 and IFN gamma. Our understanding of the effects of ILs has greatly increased since the discoveries of monocyte IL (called IL 1) and lymphocyte IL (called IL 2); more than 40 cytokines are now designated as ILs. Studies of transgenic or knockout mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided important information about IL and IFN functions. We discuss their signaling pathways cellular sources targets roles in immune regulation and cellular networks roles in allergy and asthma and roles in defense against infections. (J Allergy Clin Immunol 2011;127:701 21.)

Published
2012

37. Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products

Author

Bonertz, A., primary, Roberts, G. C., additional, Hoefnagel, M., additional, Timon, M., additional, Slater, J. E., additional, Rabin, R. L., additional, Bridgewater, J., additional, Pini, C., additional, Pfaar, O., additional, Akdis, C., additional, Goldstein, J., additional, Poulsen, L. K., additional, van Ree, R., additional, Rhyner, C., additional, Barber, D., additional, Palomares, O., additional, Sheikh, A., additional, Pawankar, R., additional, Hamerlijnk, D., additional, Klimek, L., additional, Agache, I., additional, Angier, E., additional, Casale, T., additional, Fernandez‐Rivas, M., additional, Halken, S., additional, Jutel, M., additional, Lau, S., additional, Pajno, G., additional, Sturm, G., additional, Varga, E. M., additional, Gerth van Wijk, R., additional, Bonini, S., additional, Muraro, A., additional, and Vieths, S., additional

Published
2017
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39. Global Allergy Forum and 3rd Davos Declaration 2015: Atopic dermatitis/Eczema: Challenges and opportunities toward precision medicine

Author

MS Dermatologie/Allergologie, Infection & Immunity, CDL Celdiagnostiek, Bieber, T., Akdis, C., Lauener, R., Traidl-Hoffmann, C., Schmid-Grendelmeier, P., Schäppi, G., Allam, J. P., Apfelbacher, C., Augustin, M., Beck, L., Biedermann, T., Braun-Fahrländer, C., Chew, F. T., Clavel, T., Crameri, R., Darsow, U., Deleuran, M., Dittlein, D., Duchna, H. W., Eichenfeld, L., Eyerich, K., Frei, R., Gelmetti, C., Gieler, U., Gilles, S., Glatz, M., Grando, K., Green, J., Gutermuth, J., Guttman-Yassky, E., Hanifin, J., Hijnen, D., Hoetzenecker, W., Irvine, A., Kalweit, A., Katoh, N., Knol, E, Koren, H., Möhrenschlager, M., Münch, D., Novak, N., O'Mahony, L., Paller, A. S., Rhyner, C., Roduit, C., Schiesser, K., Schröder, J., Simon, D., Simon, H. U., Sokolowska, M., Spuls, P., Stalder, J. F., Straub, D., Szalai, Z., Taieb, A., Takaoka, R., Todd, G., Todorova, A., Vestergaard, C., Werfel, T., Wollenberg, A., Ring, J., MS Dermatologie/Allergologie, Infection & Immunity, CDL Celdiagnostiek, Bieber, T., Akdis, C., Lauener, R., Traidl-Hoffmann, C., Schmid-Grendelmeier, P., Schäppi, G., Allam, J. P., Apfelbacher, C., Augustin, M., Beck, L., Biedermann, T., Braun-Fahrländer, C., Chew, F. T., Clavel, T., Crameri, R., Darsow, U., Deleuran, M., Dittlein, D., Duchna, H. W., Eichenfeld, L., Eyerich, K., Frei, R., Gelmetti, C., Gieler, U., Gilles, S., Glatz, M., Grando, K., Green, J., Gutermuth, J., Guttman-Yassky, E., Hanifin, J., Hijnen, D., Hoetzenecker, W., Irvine, A., Kalweit, A., Katoh, N., Knol, E, Koren, H., Möhrenschlager, M., Münch, D., Novak, N., O'Mahony, L., Paller, A. S., Rhyner, C., Roduit, C., Schiesser, K., Schröder, J., Simon, D., Simon, H. U., Sokolowska, M., Spuls, P., Stalder, J. F., Straub, D., Szalai, Z., Taieb, A., Takaoka, R., Todd, G., Todorova, A., Vestergaard, C., Werfel, T., Wollenberg, A., and Ring, J.

Published
2016

40. Clinical and translational allergy / Research needs in allergy: an EAACI position paper, in collaboration with EFA

Author

Papadopoulos, Nikos G., Agache, I., Bavbek, S., Bilo, B. M., Braido, F., Cardona, V., Custovic, A., Demonchy, J., Demoly, P., Eigenmann, P., Gayraud, J., Grattan, C., Heffler, E., Hellings, P. W., Jutel, M., Knol, E., Lotvall, J., Muraro, A., Poulsen, L. K., Roberts, G., Schmid-Grendelmeier, P., Skevaki, C., Triggiani, M., Vanree, R., Werfel, T., Flood, B., Palkonen, S., Savli, R., Allegri, P., Annesi-Maesano, I., Annunziato, F., Antolin-Amerigo, D., Apfelbacher, C., Blanca, M., Bogacka, E., Bonadonna, P., Bonini, M., Boyman, O., Brockow, K., Burney, P., Buters, J., Butiene, I., Calderon, M., Cardell, L. O., Caubet, J. C., Celenk, S., Cichocka-Jarosz, E., Cingi, C., Couto, M., Dejong, N., Del Giacco, S., Douladiris, N., Fassio, F., Fauquert, J. L., Fernandez, J., Rivas, M. F., Ferrer, M., Flohr, C., Gardner, J., Genuneit, J., Gevaert, P., Groblewska, A., Hamelmann, E., Hoffmann, H. J., Hoffmann-Sommergruber, K., Hovhannisyan, L., Hox, V., Jahnsen, F. L., Kalayci, O., Kalpaklioglu, A. F., Kleine-Tebbe, J., Konstantinou, G., Kurowski, M., Lau, S., Lauener, R., Lauerma, A., Logan, K., Magnan, A., Makowska, J., Makrinioti, H., Mangina, P., Manole, F., Mari, A., Mazon, A., Mills, C., Mingomataj, E., Niggemann, B., Nilsson, G., Ollert, M., O'Mahony, L., O'Neil, S., Pala, G., Papi, A., Passalacqua, G., Perkin, M., Pfaar, O., Pitsios, C., Quirce, S., Raap, U., Raulf-Heimsoth, M., Rhyner, C., Robson-Ansley, P., Alves, R. R., Roje, Z., Rondon, C., Rudzeviciene, O., Rueff, F., Rukhadze, M., Rumi, G., Sackesen, C., Santos, A. F., Santucci, A., Scharf, C., Schmidt-Weber, C., Schnyder, B., Schwarze, J., Senna, G., Sergejeva, S., Seys, S., Siracusa, A., Skypala, I., Sokolowska, M., Spertini, F., Spiewak, R., Sprikkelman, A., Sturm, G., Swoboda, Ines, Terreehorst, I., Toskala, E., Traidl-Hoffmann, C., Venter, C., Vlieg-Boerstra, B., Whitacker, P., Worm, M., Xepapadaki, P., and Akdis, C. A.

Published
2012

41. Research needs in allergy: An EAACI position paper, in collaboration with EFA

Author

Papadopoulos, N.G. Agache, I. Bavbek, S. Bilo, B.M. Braido, F. Cardona, V. Custovic, A. DeMonchy, J. Demoly, P. Eigenmann, P. Gayraud, J. Grattan, C. Heffler, E. Hellings, P.W. Jutel, M. Knol, E. Lötvall, J. Muraro, A. Poulsen, L.K. Roberts, G. Schmid-Grendelmeier, P. Skevaki, C. Triggiani, M. VanRee, R. Werfel, T. Flood, B. Palkonen, S. Savli, R. Allegri, P. Annesi-Maesano, I. Annunziato, F. Antolin-Amerigo, D. Apfelbacher, C. Blanca, M. Bogacka, E. Bonadonna, P. Bonini, M. Boyman, O. Brockow, K. Burney, P. Buters, J. Butiene, I. Calderon, M. Cardell, L.O. Caubet, J.-C. Celenk, S. Cichocka-Jarosz, E. Cingi, C. Couto, M. DeJong, N. Del Giacco, S. Douladiris, N. Fassio, F. Fauquert, J.-L. Fernandez, J. Rivas, M.F. Ferrer, M. Flohr, C. Gardner, J. Genuneit, J. Gevaert, P. Groblewska, A. Hamelmann, E. Hoffmann, H.J. Hoffmann-Sommergruber, K. Hovhannisyan, L. Hox, V. Jahnsen, F.L. Kalayci, Ö. Kalpaklioglu, A.F. Kleine-Tebbe, J. Konstantinou, G. Kurowski, M. Lau, S. Lauener, R. Lauerma, A. Logan, K. Magnan, A. Makowska, J. Makrinioti, H. Mangina, P. Manole, F. Mari, A. Mazon, A. Mills, C. Mingomataj, E.Ç. Niggemann, B. Nilsson, G. Ollert, M. O'Mahony, L. O'Neil, S. Pala, G. Papi, A. Passalacqua, G. Perkin, M. Pfaar, O. Pitsios, C. Quirce, S. Raap, U. Raulf-Heimsoth, M. Rhyner, C. Robson-Ansley, P. Alves, R.R. Roje, Z. Rondon, C. Rudzeviciene, O. Ruëff, F. Rukhadze, M. Rumi, G. Sackesen, C. Santos, A.F. Santucci, A. Scharf, C. Schmidt-Weber, C. Schnyder, B. Schwarze, J. Senna, G. Sergejeva, S. Seys, S. Siracusa, A. Skypala, I. Sokolowska, M. Spertini, F. Spiewak, R. Sprikkelman, A. Sturm, G. Swoboda, I. Terreehorst, I. Toskala, E. Traidl-Hoffmann, C. Venter, C. Vlieg-Boerstra, B. Whitacker, P. Worm, M. Xepapadaki, P. Akdis, C.A.

Abstract

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century. The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels. Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein. © 2012 Papadopoulos et al.

Published
2012

49. Research needs in allergy: An EAACI position paper, in collaboration with EFA

Author

Papadopoulos, N., Agache, I., Bavbek, S. (Sevim), Bilo, B.M. (Beatrice M.), Braido, F. (Fulvio), Cardona, D. (Doris), Custovic, A. (Adnan), DeMonchy, J. (Jan), Demoly, P., Eigenmann, P.A. (Philippe), Gayraud, J. (J.), Grattan, C., Heffler, E. (E.), Hellings, P.W. (Peter), Jutel, M. (M.), Knol, E.F. (Edward Frank), Lötvall, J. (Jan), Murarol, A. (Antonella), Poulsen, L.K., Roberts, G., Schmid-Grendelmeier, P. (Peter), Skevaki, C. (Chrysanthi), Triggiani, M. (M.), VanRee, R. (Ronald), Werfel, T., Flood, B. (Breda), Palkonen, S., Savli, R. (Roberta), Allegri, P. (Pia), Annesi-Maesano, I. (Isabella), Annunziato, F. (Francesco), Antolin-Amerigo, D. (Dario), Apfelbacher, M. (Manuela), Blanca, M. (Miguel), Bogacka, E. (Ewa), Bonadonna, P. (Patrizia), Bonini, M. (Matteo), Boyman, O. (Onur), Brockow, K. (Knut), Burney, P. (Peter), Buters, J. (Jeroen), Butiene, I. (Indre), Calderon, M. (Moises), Cardell, L.O., Caubet, J.-C. (Jean-Christoph), Celenk, S. (Sevcan), Cichocka-Jarosz, E., Cingi, C. (Cemal), Couto, M. (Mariana), DeJong, N. (Nicolette), Del Giacco, S. (Stefano), Douladiris, N. (Nikolaos), Fassio, F. (Filippo), Fauquert, J.-L. (Jean-Luc), Fernandez, J. (Javier), Rivas, M.F. (Montserrat Fernandez), Ferrer, M. (Marta), Flohr, C. (Carsten), Gardner, J. (James), Genuneit, J. (Jon), Gevaert, P. (P.), Groblewska, A. (Anna), Hamelmann, E. (Eckard), Hoffmann, H.J. (Hans Jürgen), Hoffmann-Sommergruber, K. (K.), Hovhannisyan, L. (Lilit), Hox, V. (Valérie), Jahnsen, F.L. (Frode L.), Kalayci, O. (Omer), Kalpaklioglu, A.F. (Ayse Füsun), Kleine-Tebbe, J. (Jörg), Konstantinou, G. (George), Kurowski, M. (Marcin), Lau, S. (Susanne), Lauener, R. (Roger), Lauerma, A. (Antti), Logan, K. (K.), Magnan, A. (Antoine), Makowska, J. (Joanna), Makrinioti, H. (Heidi), Mangina, P. (Paraskevi), Manole, F. (Felicia), Mari, A. (A.), Mazón, A., Mills, C. (Clare), Mingomataj, E.Ç. (Ervin Ç), Niggemann, B., Nilsson, G. (Gunnar), Ollert, M. (Markus), O'Mahony, L. (Liam), O'Neil, S. (Serena), Pala, G. (Gianni), Papi, A. (Alberto), Passalacqua, G. (Giovanni), Perkin, M. (Michael), Pfaar, O. (Oliver), Pitsios, C., Quirce, S. (S.), Raap, U., Raulf-Heimsoth, M., Rhyner, C. (Claudio), Robson-Ansley, P. (Paula), Alves, R.R. (Rodrigo Rodrigues), Roje, Z. (Zeljka), Rondon, C. (Carmen), Rudzeviciene, O. (Odilija), Rueff, F. (Franziska), Rukhadze, M. (Maia), Rumi, G. (Gabriele), Sackesen, C. (Cansin), Santos, A.F. (Alexandra F.), Santucci, A. (Annalisa), Scharf, C. (Christian), Schmidt-Weber, C.B., Schnyder, B. (Benno), Schwarze, J. (Jürgen), Senna, G.E. (Gianenrico), Sergejeva, S. (Svetlana), Seys, S. (Sven), Siracusa, A. (Andrea), Skypala, I. (I.), Sokolowska, M. (Milena), Spertini, F. (Francois), Spiewak, R. (Radoslaw), Sprikkelman, A.B. (Aline), Sturm, G.J., Swoboda, I., Terreehorst, I., Toskala, E., Traidl-Hoffmann, C. (Claudia), Venter, C. (C.), Vlieg-Boerstra, B.J., Whitacker, P. (Paul), Worm, M. (M.), Xepapadaki, P. (Paraskevi), Akdis, C.A., Papadopoulos, N., Agache, I., Bavbek, S. (Sevim), Bilo, B.M. (Beatrice M.), Braido, F. (Fulvio), Cardona, D. (Doris), Custovic, A. (Adnan), DeMonchy, J. (Jan), Demoly, P., Eigenmann, P.A. (Philippe), Gayraud, J. (J.), Grattan, C., Heffler, E. (E.), Hellings, P.W. (Peter), Jutel, M. (M.), Knol, E.F. (Edward Frank), Lötvall, J. (Jan), Murarol, A. (Antonella), Poulsen, L.K., Roberts, G., Schmid-Grendelmeier, P. (Peter), Skevaki, C. (Chrysanthi), Triggiani, M. (M.), VanRee, R. (Ronald), Werfel, T., Flood, B. (Breda), Palkonen, S., Savli, R. (Roberta), Allegri, P. (Pia), Annesi-Maesano, I. (Isabella), Annunziato, F. (Francesco), Antolin-Amerigo, D. (Dario), Apfelbacher, M. (Manuela), Blanca, M. (Miguel), Bogacka, E. (Ewa), Bonadonna, P. (Patrizia), Bonini, M. (Matteo), Boyman, O. (Onur), Brockow, K. (Knut), Burney, P. (Peter), Buters, J. (Jeroen), Butiene, I. (Indre), Calderon, M. (Moises), Cardell, L.O., Caubet, J.-C. (Jean-Christoph), Celenk, S. (Sevcan), Cichocka-Jarosz, E., Cingi, C. (Cemal), Couto, M. (Mariana), DeJong, N. (Nicolette), Del Giacco, S. (Stefano), Douladiris, N. (Nikolaos), Fassio, F. (Filippo), Fauquert, J.-L. (Jean-Luc), Fernandez, J. (Javier), Rivas, M.F. (Montserrat Fernandez), Ferrer, M. (Marta), Flohr, C. (Carsten), Gardner, J. (James), Genuneit, J. (Jon), Gevaert, P. (P.), Groblewska, A. (Anna), Hamelmann, E. (Eckard), Hoffmann, H.J. (Hans Jürgen), Hoffmann-Sommergruber, K. (K.), Hovhannisyan, L. (Lilit), Hox, V. (Valérie), Jahnsen, F.L. (Frode L.), Kalayci, O. (Omer), Kalpaklioglu, A.F. (Ayse Füsun), Kleine-Tebbe, J. (Jörg), Konstantinou, G. (George), Kurowski, M. (Marcin), Lau, S. (Susanne), Lauener, R. (Roger), Lauerma, A. (Antti), Logan, K. (K.), Magnan, A. (Antoine), Makowska, J. (Joanna), Makrinioti, H. (Heidi), Mangina, P. (Paraskevi), Manole, F. (Felicia), Mari, A. (A.), Mazón, A., Mills, C. (Clare), Mingomataj, E.Ç. (Ervin Ç), Niggemann, B., Nilsson, G. (Gunnar), Ollert, M. (Markus), O'Mahony, L. (Liam), O'Neil, S. (Serena), Pala, G. (Gianni), Papi, A. (Alberto), Passalacqua, G. (Giovanni), Perkin, M. (Michael), Pfaar, O. (Oliver), Pitsios, C., Quirce, S. (S.), Raap, U., Raulf-Heimsoth, M., Rhyner, C. (Claudio), Robson-Ansley, P. (Paula), Alves, R.R. (Rodrigo Rodrigues), Roje, Z. (Zeljka), Rondon, C. (Carmen), Rudzeviciene, O. (Odilija), Rueff, F. (Franziska), Rukhadze, M. (Maia), Rumi, G. (Gabriele), Sackesen, C. (Cansin), Santos, A.F. (Alexandra F.), Santucci, A. (Annalisa), Scharf, C. (Christian), Schmidt-Weber, C.B., Schnyder, B. (Benno), Schwarze, J. (Jürgen), Senna, G.E. (Gianenrico), Sergejeva, S. (Svetlana), Seys, S. (Sven), Siracusa, A. (Andrea), Skypala, I. (I.), Sokolowska, M. (Milena), Spertini, F. (Francois), Spiewak, R. (Radoslaw), Sprikkelman, A.B. (Aline), Sturm, G.J., Swoboda, I., Terreehorst, I., Toskala, E., Traidl-Hoffmann, C. (Claudia), Venter, C. (C.), Vlieg-Boerstra, B.J., Whitacker, P. (Paul), Worm, M. (M.), Xepapadaki, P. (Paraskevi), and Akdis, C.A.

Abstract

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century. The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels. Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and tre

Published
2012
Full Text
View/download PDF

50. In vitro evolution of allergy vaccine candidates, with maintained structure, but reduced B cell and T cell activation capacity

Author

Nilsson, O B, Adedoyin, J, Rhyner, C, Neimert-Andersson, T, Grundström, J, Berndt, K D, Crameri, R, Grönlund, H, Nilsson, O B, Adedoyin, J, Rhyner, C, Neimert-Andersson, T, Grundström, J, Berndt, K D, Crameri, R, and Grönlund, H

Abstract

Allergy and asthma to cat (Felis domesticus) affects about 10% of the population in affluent countries. Immediate allergic symptoms are primarily mediated via IgE antibodies binding to B cell epitopes, whereas late phase inflammatory reactions are mediated via activated T cell recognition of allergen-specific T cell epitopes. Allergen-specific immunotherapy relieves symptoms and is the only treatment inducing a long-lasting protection by induction of protective immune responses. The aim of this study was to produce an allergy vaccine designed with the combined features of attenuated T cell activation, reduced anaphylactic properties, retained molecular integrity and induction of efficient IgE blocking IgG antibodies for safer and efficacious treatment of patients with allergy and asthma to cat. The template gene coding for rFel d 1 was used to introduce random mutations, which was subsequently expressed in large phage libraries. Despite accumulated mutations by up to 7 rounds of iterative error-prone PCR and biopanning, surface topology and structure was essentially maintained using IgE-antibodies from cat allergic patients for phage enrichment. Four candidates were isolated, displaying similar or lower IgE binding, reduced anaphylactic activity as measured by their capacity to induce basophil degranulation and, importantly, a significantly lower T cell reactivity in lymphoproliferative assays compared to the original rFel d 1. In addition, all mutants showed ability to induce blocking antibodies in immunized mice.The approach presented here provides a straightforward procedure to generate a novel type of allergy vaccines for safer and efficacious treatment of allergic patients.

Published
2011

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