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7. Activation of the aryl hydrocarbon receptor improves allergen-specific immunotherapy of murine allergic airway inflammation: a novel adjuvant option?

Author

Heine, Sonja, Alessandrini, Francesca, Grosch, Johannes, Graß, Carina, Heldner, Alexander, Schnautz, Benjamin, Grosch, Johanna, Buters, Jeroen, Slusarenko, Benjamin O., Krappmann, Daniel, Fallarino, Francesca, Ohnmacht, Caspar, Schmidt-Weber, Carsten B., and Blank, Simon

Subjects
ARYL hydrocarbon receptors, TRANSCRIPTION factors, TREATMENT effectiveness, IMMUNOTHERAPY, TH2 cells
Abstract

Background: Allergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed. Methods: Amurinemodel of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7Hbenzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome. Results: Although AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhRdependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels. Conclusion: This study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT. [ABSTRACT FROM AUTHOR]

Published
2024
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15. EAACI Molecular Allergology User's Guide 2.0

Author

Dramburg, Stephanie, primary, Hilger, Christiane, additional, Santos, Alexandra F., additional, de las Vecillas, Leticia, additional, Aalberse, Rob C., additional, Acevedo, Nathalie, additional, Aglas, Lorenz, additional, Altmann, Friedrich, additional, Arruda, Karla L., additional, Asero, Riccardo, additional, Ballmer‐Weber, Barbara, additional, Barber, Domingo, additional, Beyer, Kirsten, additional, Biedermann, Tilo, additional, Bilo, Maria Beatrice, additional, Blank, Simon, additional, Bosshard, Philipp P., additional, Breiteneder, Heimo, additional, Brough, Helen A., additional, Bublin, Merima, additional, Campbell, Dianne, additional, Caraballo, Luis, additional, Caubet, Jean Christoph, additional, Celi, Giorgio, additional, Chapman, Martin D., additional, Chruszcz, Maksymilian, additional, Custovic, Adnan, additional, Czolk, Rebecca, additional, Davies, Janet, additional, Douladiris, Nikolaos, additional, Eberlein, Bernadette, additional, Ebisawa, Motohiro, additional, Ehlers, Anna, additional, Eigenmann, Philippe, additional, Gadermaier, Gabriele, additional, Giovannini, Mattia, additional, Gomez, Francisca, additional, Grohman, Rebecca, additional, Guillet, Carole, additional, Hafner, Christine, additional, Hamilton, Robert G., additional, Hauser, Michael, additional, Hawranek, Thomas, additional, Hoffmann, Hans Jürgen, additional, Holzhauser, Thomas, additional, Iizuka, Tomona, additional, Jacquet, Alain, additional, Jakob, Thilo, additional, Janssen‐Weets, Bente, additional, Jappe, Uta, additional, Jutel, Marek, additional, Kalic, Tanja, additional, Kamath, Sandip, additional, Kespohl, Sabine, additional, Kleine‐Tebbe, Jörg, additional, Knol, Edward, additional, Knulst, André, additional, Konradsen, Jon R., additional, Korošec, Peter, additional, Kuehn, Annette, additional, Lack, Gideon, additional, Le, Thuy‐My, additional, Lopata, Andreas, additional, Luengo, Olga, additional, Mäkelä, Mika, additional, Marra, Alessandro Maria, additional, Mills, Clare, additional, Morisset, Martine, additional, Muraro, Antonella, additional, Nowak‐Wegrzyn, Anna, additional, Nugraha, Roni, additional, Ollert, Markus, additional, Palosuo, Kati, additional, Pastorello, Elide Anna, additional, Patil, Sarita Ulhas, additional, Platts‐Mills, Thomas, additional, Pomés, Anna, additional, Poncet, Pascal, additional, Potapova, Ekaterina, additional, Poulsen, Lars K., additional, Radauer, Christian, additional, Radulovic, Suzana, additional, Raulf, Monika, additional, Rougé, Pierre, additional, Sastre, Joaquin, additional, Sato, Sakura, additional, Scala, Enrico, additional, Schmid, Johannes M., additional, Schmid‐Grendelmeier, Peter, additional, Schrama, Denise, additional, Sénéchal, Hélène, additional, Traidl‐Hoffmann, Claudia, additional, Valverde‐Monge, Marcela, additional, van Hage, Marianne, additional, van Ree, Ronald, additional, Verhoeckx, Kitty, additional, Vieths, Stefan, additional, Wickman, Magnus, additional, Zakzuk, Josefina, additional, Matricardi, Paolo M., additional, and Hoffmann‐Sommergruber, Karin, additional

Published
2023
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19. A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteria

Author

Kreft, Luisa, primary, Schepers, Aloys, additional, Hils, Miriam, additional, Swiontek, Kyra, additional, Flatley, Andrew, additional, Janowski, Robert, additional, Mirzaei, Mohammadali Khan, additional, Dittmar, Michael, additional, Chakrapani, Neera, additional, Desai, Mahesh S., additional, Eyerich, Stefanie, additional, Deng, Li, additional, Niessing, Dierk, additional, Fischer, Konrad, additional, Feederle, Regina, additional, Blank, Simon, additional, Schmidt-Weber, Carsten B., additional, Hilger, Christiane, additional, Biedermann, Tilo, additional, and Ohnmacht, Caspar, additional

Published
2022
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20. α-Gal present on both glycolipids and glycoproteins contributes to immune response in meat-allergic patients

Author

Chakrapani, Neera, primary, Fischer, Jörg, additional, Swiontek, Kyra, additional, Codreanu-Morel, Françoise, additional, Hannachi, Farah, additional, Morisset, Martine, additional, Mugemana, Clément, additional, Bulaev, Dmitry, additional, Blank, Simon, additional, Bindslev-Jensen, Carsten, additional, Biedermann, Tilo, additional, Ollert, Markus, additional, and Hilger, Christiane, additional

Published
2022
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21. Thermosensitive PLGA–PEG–PLGA Hydrogel as Depot Matrix for Allergen-Specific Immunotherapy

Author

Heine, Sonja, primary, Aguilar-Pimentel, Antonio, additional, Russkamp, Dennis, additional, Alessandrini, Francesca, additional, Gailus-Durner, Valerie, additional, Fuchs, Helmut, additional, Ollert, Markus, additional, Bredehorst, Reinhard, additional, Ohnmacht, Caspar, additional, Zissler, Ulrich M., additional, Hrabě de Angelis, Martin, additional, Schmidt-Weber, Carsten B., additional, and Blank, Simon, additional

Published
2022
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24. Allergen Content of Therapeutic Preparations for Allergen-Specific Immunotherapy of European Paper Wasp Venom Allergy

Author

Grosch, Johannes, primary, Lesur, Antoine, additional, Kler, Stéphanie, additional, Bernardin, François, additional, Dittmar, Gunnar, additional, Francescato, Elisabetta, additional, Hewings, Simon J., additional, Jakwerth, Constanze A., additional, Zissler, Ulrich M., additional, Heath, Matthew D., additional, Ollert, Markus, additional, Kramer, Matthias F., additional, Hilger, Christiane, additional, Bilò, Maria Beatrice, additional, Schmidt-Weber, Carsten B., additional, and Blank, Simon, additional

Published
2022
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25. A New Value Premium : Value Creation in the Swedish stock market

Author

Jalili, Lemar, Blank, Simon, and Höög, Samuel

Subjects
Fama and French three-factor model, ROIC, WACC, ROIC-WACC Spread, Asset-pricing models, Value creation, Factor models, Value Premium, Business Administration, Företagsekonomi
Abstract

Value creation in any stock market is a highly discussed topic with an abundant amount of generalized models aiming to predict future returns. Although no such tool exists yet there are, however, acknowledged models from peer-reviewed journals that have received a lot of attention over the years in examining company performance. This thesis is therefore built on the well-known Fama-French three-factor model. The original Fama-French three-factor model is extended by adding a new size premium and a new value premium, both based upon the spread between the return on invested capital (ROIC) – the weighted average cost of capital (WACC). The purpose of this is to make the returns of a portfolio account for cash flow and debt on top of risk, size, and value premium for a company. This thesis finds that the ROIC-WACC spread adds explanatory power to the existing Fama and French three-factor model on the Swedish stock market. The research method of this study is quantitative and deductive. The considered period is six years between the years 2014 and 2020.

Published
2022

27. Ex Vivo Immunomodulatory Effects of Lactobacillus-, Lacticaseibacillus-, and Bifidobacterium-Containing Synbiotics on Human Peripheral Blood Mononuclear Cells and Monocyte-Derived Dendritic Cells in the Context of Grass Pollen Allergy

Author

Heldner, Alexander, primary, Heath, Matthew D., additional, Schnautz, Benjamin, additional, Kotz, Sebastian, additional, Chaker, Adam, additional, Kramer, Matthias F., additional, Jakwerth, Constanze A., additional, Zissler, Ulrich M., additional, Schmidt-Weber, Carsten B., additional, and Blank, Simon, additional

Published
2022
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29. Venom Immunotherapy: From Proteins to Product to Patient Protection

Author

Feindor, Martin, primary, Heath, Matthew D., additional, Hewings, Simon J., additional, Carreno Velazquez, Thalia L., additional, Blank, Simon, additional, Grosch, Johannes, additional, Jakob, Thilo, additional, Schmid-Grendelmeier, Peter, additional, Klimek, Ludger, additional, Golden, David B. K., additional, Skinner, Murray A., additional, and Kramer, Matthias F., additional

Published
2021
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30. Characterization of New Allergens from the Venom of the European Paper Wasp Polistes dominula

Author

Grosch, Johannes, primary, Eberlein, Bernadette, additional, Waldherr, Sebastian, additional, Pascal, Mariona, additional, San Bartolomé, Clara, additional, De La Roca Pinzón, Federico, additional, Dittmar, Michael, additional, Hilger, Christiane, additional, Ollert, Markus, additional, Biedermann, Tilo, additional, Darsow, Ulf, additional, Bilò, Maria Beatrice, additional, Schmidt-Weber, Carsten B., additional, and Blank, Simon, additional

Published
2021
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31. Immunological effects of adjuvanted low‐dose allergoid allergen‐specific immunotherapy in experimental murine house dust mite allergy

Author

Heldner, Alexander, primary, Alessandrini, Francesca, additional, Russkamp, Dennis, additional, Heine, Sonja, additional, Schnautz, Benjamin, additional, Chaker, Adam, additional, Mwange, Juliet, additional, Carreno Velazquez, Thalia L., additional, Heath, Matthew D., additional, Skinner, Murray A., additional, Kramer, Matthias F., additional, Zissler, Ulrich M., additional, Schmidt‐Weber, Carsten B., additional, and Blank, Simon, additional

Published
2021
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33. A novel monoclonal IgG1 antibody specific for Galactosealpha- 1,3-galactose questions alpha-Gal epitope expression by bacteria.

Author

Kreft, Luisa, Schepers, Aloys, Hils, Miriam, Swiontek, Kyra, Flatley, Andrew, Janowski, Robert, Mirzaei, Mohammadali Khan, Dittmar, Michael, Chakrapani, Neera, Desai, Mahesh S., Eyerich, Stefanie, Li Deng, Niessing, Dierk, Fischer, Konrad, Feederle, Regina, Blank, Simon, Schmidt-Weber, Carsten B., Hilger, Christiane, Biedermann, Tilo, and Ohnmacht, Caspar

Abstract

The alpha-Gal epitope (α-Gal) with the determining element galactose-α1,3-galactose can lead to clinically relevant allergic reactions and rejections in xenotransplantation. These immune reactions can develop because humans are devoid of this carbohydrate due to evolutionary loss of the enzyme α1,3-galactosyltransferase (GGTA1). In addition, up to 1% of human IgG antibodies are directed against α-Gal, but the stimulus for the induction of anti-α-Gal antibodies is still unclear. Commensal bacteria have been suggested as a causal factor for this induction as α-Gal binding tools such as lectins were found to stain cultivated bacteria isolated from the intestinal tract. Currently available tools for the detection of the definite α-Gal epitope, however, are cross-reactive, or have limited affinity and, hence, offer restricted possibilities for application. In this study, we describe a novel monoclonal IgG1 antibody (27H8) specific for the α-Gal epitope. The 27H8 antibody was generated by immunization of Ggta1 knockout mice and displays a high affinity towards synthetic and naturally occurring α-Gal in various applications. Using this novel tool, we found that intestinal bacteria reported to be α-Gal positive cannot be stained with 27H8 questioning whether commensal bacteria express the native α-Gal epitope at all. [ABSTRACT FROM AUTHOR]

Published
2022
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35. An exhausted phenotype of TH2 cells is primed by allergen exposure, but not reinforced by allergen‐specific immunotherapy

Author

Wang, Shu‐Hung, primary, Zissler, Ulrich M., additional, Buettner, Maren, additional, Heine, Sonja, additional, Heldner, Alexander, additional, Kotz, Sebastian, additional, Pechtold, Lisa, additional, Kau, Josephine, additional, Plaschke, Mirjam, additional, Ullmann, Julia T., additional, Guerth, Ferdinand, additional, Oelsner, Madlen, additional, Alessandrini, Francesca, additional, Blank, Simon, additional, Chaker, Adam M., additional, Schmidt‐Weber, Carsten B., additional, and Jakwerth, Constanze A., additional

Published
2021
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42. Comprehensive mapping of immune tolerance yields a regulatory TNF receptor 2 signature in a murine model of successful Fel d 1‐specific immunotherapy using high‐dose CpG adjuvant

Author

Leonard, Cathy, primary, Montamat, Guillem, additional, Davril, Caroline, additional, Domingues, Olivia, additional, Hunewald, Oliver, additional, Revets, Dominique, additional, Guerin, Coralie, additional, Blank, Simon, additional, Heckendorn, Justine, additional, Jardon, Gauthier, additional, Hentges, François, additional, and Ollert, Markus, additional

Published
2021
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47. Immunological effects of adjuvanted low‐dose allergoid allergen‐specific immunotherapy in experimental murine house dust mite allergy.

Author

Heldner, Alexander, Alessandrini, Francesca, Russkamp, Dennis, Heine, Sonja, Schnautz, Benjamin, Chaker, Adam, Mwange, Juliet, Carreno Velazquez, Thalia L., Heath, Matthew D., Skinner, Murray A., Kramer, Matthias F., Zissler, Ulrich M., Schmidt‐Weber, Carsten B., and Blank, Simon

Subjects
HOUSE dust mites, ALLERGENIC extracts, ALLERGIES, THERAPEUTICS, IMMUNOTHERAPY
Abstract

Background: Native allergen extracts or chemically modified allergoids are routinely used to induce allergen tolerance in allergen‐specific immunotherapy (AIT), although mechanistic side‐by‐side studies are rare. It is paramount to balance optimal dose and allergenicity to achieve efficacy warranting safety. AIT safety and efficacy could be addressed by allergen dose reduction and/or use of allergoids and immunostimulatory adjuvants, respectively. In this study, immunological effects of experimental house dust mite (HDM) AIT were investigated applying high‐dose HDM extract and low‐dose HDM allergoids with and without the adjuvants microcrystalline tyrosine (MCT) and monophosphoryl lipid A (MPL) in a murine model of HDM allergy. Methods: Cellular, humoral, and clinical effects of the different AIT strategies were assessed applying a new experimental AIT model of murine allergic asthma based on physiological, adjuvant‐free intranasal sensitization followed by subcutaneous AIT. Results: While low‐dose allergoid and high‐dose extract AIT demonstrated comparable potency to suppress allergic airway inflammation and Th2‐type cytokine secretion of lung‐resident lymphocytes and draining lymph node cells, low‐dose allergoid AIT was less effective in inducing a potentially protective IgG1 response. Combining low‐dose allergoid AIT with MCT or MCT and dose‐adjusted MPL promoted Th1‐inducing mechanisms and robust B‐cell activation counterbalancing the allergic Th2 immune response. Conclusion: Low allergen doses induce cellular and humoral mechanisms counteracting Th2‐driven inflammation by using allergoids and dose‐adjusted adjuvants. In light of safety and efficacy improvement, future therapeutic approaches may use low‐dose allergoid strategies to drive cellular tolerance and adjuvants to modulate humoral responses. [ABSTRACT FROM AUTHOR]

Published
2022
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