A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy Fatimah Kussebi, MD, Fariba Karamloo, PhD, Claudio Rhyner,

Slides:

Advertisements

Similar presentations

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

Advertisements

TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert.

Peter Vadas, MD, PhD, Boris Perelman, PhD, Gary Liss, MD, MS

Triggering of specific Toll-like receptors and proinflammatory cytokines breaks allergen- specific T-cell tolerance in human tonsils and peripheral blood

Early suppression of basophil activation during allergen-specific immunotherapy by histamine receptor 2 Natalija Novak, MD, Nihal Mete, MD, Caroline.

Kuan-Wei Chen, PhD, Katharina Blatt, MSc, Wayne R

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema Sabine Zeller, MSc, Claudio Rhyner, PhD, Norbert Meyer, MD, Peter.

The effects of upper respiratory infection on T-cell proliferation and steroid sensitivity of asthmatics Elcio O. Vianna, MD, PhD, Jay Westcott, PhD,

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

Differential cytokine induction by the human skin–associated autoallergen thioredoxin in sensitized patients with atopic dermatitis and healthy control.

Development and characterization of a recombinant, hypoallergenic, peptide-based vaccine for grass pollen allergy Margarete Focke-Tejkl, PhD, Milena.

Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy Raphaela.

IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis Norbert Meyer, MD, Maya Zimmermann, PhD,

Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis Lisa M. Bartnikas, MD, Michael F. Gurish,

Malassezia sympodialis thioredoxin–specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis Hari Balaji, MSc, Annice Heratizadeh,

Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity: Role of macrophage scavenger receptor class A type I and II

Birch pollen immunotherapy results in long-term loss of Bet v 1–specific TH2 responses, transient TR1 activation, and synthesis of IgE-blocking antibodies

Is 9 more than 2 also in allergic airway inflammation?

Rush immunotherapy results in allergen-specific alterations in lymphocyte function and interferon-γ production in CD4+ T cells Gideon Lack, MD, Harold.

Characterization of pollen antigen–induced IL-31 production by PBMCs in patients with allergic rhinitis Mitsuhiro Okano, MD, Tazuko Fujiwara, BS, Takaya.

IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain— containing protein tyrosine phosphatase 1 Alison Taylor, PhD, Mübeccel.

Triggering of specific Toll-like receptors and proinflammatory cytokines breaks allergen- specific T-cell tolerance in human tonsils and peripheral blood

Histamine in the immune regulation of allergic inflammation

Toll-like receptor 9 suppression in plasmacytoid dendritic cells after IgE-dependent activation is mediated by autocrine TNF-α John T. Schroeder, PhD,

TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert.

Staphylococcus aureus fibronectin-binding protein specifically binds IgE from patients with atopic dermatitis and requires antigen presentation for cellular.

A fusion protein of flagellin and ovalbumin suppresses the TH2 response and prevents murine intestinal allergy Stefan Schülke, PhD, Manja Burggraf, MSc,

Regulation of allergic airway inflammation by class I–restricted allergen presentation and CD8 T-cell infiltration James W. Wells, PhD, Christopher J.

Patients with atopic dermatitis and history of eczema herpeticum elicit herpes simplex virus–specific type 2 immune responses Stephan Traidl, Petra Kienlin,

T Cell Epitope-Specific Defects in the Immune Response to Cat Allergen in Patients with Atopic Dermatitis Raquel Carneiro, Amanda Reefer, Barbara Wilson,

Inhibition of angiogenesis by IL-32: Possible role in asthma

Activin A is an acute allergen-responsive cytokine and provides a link to TGF-β– mediated airway remodeling in asthma Christian Karagiannidis, MD, Gabriele.

Identification of bee venom Api m 1 IgE epitopes and characterization of corresponding mimotopes Abida Zahirović, MPharm, Ana Koren, PhD, Peter Kopač,

Protein unfolding strongly modulates the allergenicity and immunogenicity of Pru p 3, the major peach allergen Masako Toda, PhD, Gerald Reese, PhD, Gabriele.

Characterization of the allergic T-cell response to Pru p 3, the nonspecific lipid transfer protein in peach Véronique Schulten, MSc, Astrid Radakovics,

Genetically engineered hybrid proteins from Parietaria judaica pollen for allergen- specific immunotherapy Roberto González-Rioja, PhD, Ignacio Ibarrola,

The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4+ or CD8+ T cells Juha Punnonen, MD, PhD, Hans Yssel, PhD,

A hypoallergenic variant of Der p 1 as a candidate for mite allergy vaccines David Walgraffe, PhD, Christel Mattéotti, PhD, Mohamed el Bakkoury, PhD,

Peter Vadas, MD, PhD, Boris Perelman, PhD, Gary Liss, MD, MS

Claus Bachert, MD, PhD, Cezmi A. Akdis, MD

Kuan-Wei Chen, PhD, Katharina Blatt, MSc, Wayne R

IL-12 affects Dermatophagoides farinae–induced IL-4 production by T cells from pediatric patients with mite-sensitive asthma Takeshi Noma, MD, PhD, Izumi.

Liam O’Mahony, PhD, Mübeccel Akdis, MD, PhD, Cezmi A. Akdis, MD

Impaired intestinal tolerance in the absence of a functional complement system Pirkka T. Pekkarinen, MD, Kirsi Vaali, PhD, Hanna Jarva, MD, PhD, Eliisa.

Tuure Kinnunen, MD, Kalle Jutila, BM, William W

Immune response modifiers in the treatment of asthma: A PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy.

Enhanced production of CCL18 by tolerogenic dendritic cells is associated with inhibition of allergic airway reactivity Iris Bellinghausen, PhD, Sebastian.

Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice Jianing Li, MS, Yu Wang,

TH1-promoting DNA immunization against allergens modulates the ratio of IgG1/IgG2a but does not affect the anaphylactic potential of IgG1 antibodies

Association between specific timothy grass antigens and changes in TH1- and TH2-cell responses following specific immunotherapy Véronique Schulten, PhD,

A hypoallergenic cat vaccine based on Fel d 1–derived peptides fused to hepatitis B PreS Katarzyna Niespodziana, MSc, Margarete Focke-Tejkl, PhD, Birgit.

Harald Renz, MD, Chaya Brodie, PhD, Katherine Bradley, BS, Donald Y. M

Mechanisms of allergen-specific desensitization

Antigen coupled with Lewis-x trisaccharides elicits potent immune responses in mice Shih-Chang Hsu, BS, Tsung-Hsien Tsai, MD, Hirokazu Kawasaki, PhD,

Benjamin Chaigne, MD, Hervé Watier, MD, PhD

T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma Axel Trautmann, MDa, Peter Schmid-Grendelmeier, MDa,

Clinical and immunologic effects of H1 antihistamine preventive medication during honeybee venom immunotherapy Ulrich R. Müller, MD, Marek Jutel, MD,

In vivo effects of glucocorticoids on IgE production

Pedro Gamboa, MD, PhD, Rosa Sanchez-Monge, PhD, M

Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity James N. Francis, PhD, Louisa.

The IgE-Reactive Autoantigen Hom s 2 Induces Damage of Respiratory Epithelial Cells and Keratinocytes via Induction of IFN-γ Irene Mittermann, Renate.

IgE-mediated and T cell–mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis Peter Schmid-Grendelmeier, MD, Sabine Flückiger,

Gastrointestinal digestion of Bet v 1–homologous food allergens destroys their mediator- releasing, but not T cell–activating, capacity Eva Maria Schimek,

Placental transfer of allergen-specific IgG but not IgE from a specific immunotherapy– treated mother Sabine Flicker, PhD, Katharina Marth, MD, Heinz.

IgG4 production is confined to human IL-10–producing regulatory B cells that suppress antigen-specific immune responses Willem van de Veen, MSc, Barbara.

Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding Sven.

Advances and highlights in mechanisms of allergic disease in 2015

The effects of gastric digestion on codfish allergenicity

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

Presentation transcript:

A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy Fatimah Kussebi, MD, Fariba Karamloo, PhD, Claudio Rhyner, PhD, Peter Schmid-Grendelmeier, MD, Maria Salagianni, PhD, Christian Mannhart, Mübeccel Akdis, MD, PhD, Lyudmilla Soldatova, PhD, Zora Markovic-Housley, PhD, Barbara R. von Beust, PhD, Thomas Kündig, MD, David M. Kemeny, PhD, Kurt Blaser, PhD, Reto Crameri, PhD, Cezmi A. Akdis, MD Journal of Allergy and Clinical Immunology Volume 115, Issue 2, Pages 323-329 (February 2005) DOI: 10.1016/j.jaci.2004.11.041 Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 Characterization of Api m [1/2] fusion protein. A, Coomassie staining of 0.5 μmol/L recombinant Api m 1, Api m 2, and Api m [1/2] fusion protein. B, Binding of 8 different mouse anti–Api m 2 IgG mAbs to Api m 1 (lane 1), Api m 2 (lane 2), and Api m [1/2] (lane 3). C, Dot blot analysis of human anti–Api m 1 IgG4 mAb binding to Api m 1, Api m 2, and Api m [1/2]. D, Api m [1/2] does not induce IgE and IgG2a against native Api m 1. Api m 1–specific IgE and IgG2a were determined by ELISA. Journal of Allergy and Clinical Immunology 2005 115, 323-329DOI: (10.1016/j.jaci.2004.11.041) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 Low IgE binding to Api m [1/2] fusion protein. A, Serum IgE binding to BV, Api m 1, Api m 2, and the Api m [1/2] fusion protein. B, Serum IgE binding (12 different patients allergic to BV) to equimolar amounts of Api m 1, Api m 2, and Api m [1/2] coated on the solid phase by ELISA. There was no inhibition of serum IgE binding to Api m 1 (C) and Api m 2 (D) coated on a solid phase by Api m [1/2]. BSA was used as control. Journal of Allergy and Clinical Immunology 2005 115, 323-329DOI: (10.1016/j.jaci.2004.11.041) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 Reduced allergenic activity of the Api m [1/2] fusion protein. Induction of leukotriene release (A) and histamine release (B) from basophils of 3 patients allergic to BV stimulated with equimolar amounts of Api m 1, Api m 2, Api m [1/2] fusion protein, and BV. Journal of Allergy and Clinical Immunology 2005 115, 323-329DOI: (10.1016/j.jaci.2004.11.041) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 Induction of T-cell proliferation and cytokine production by Api m [1/2]. PBMCs were stimulated with equimolar amounts of Api m 1, Api m 2, and the Api m [1/2] fusion protein. Thymidine incorporation (3[H] TdR) was measured after 5 days. Background proliferation of unstimulated cultures was between 1570 and 3355 cpm. IL-4, IFN-γ, IL-13, IL-10, and IL-5 were determined in parallel culture supernatants by ELISA. Cytokine production of healthy PBMCs was less than 10% and was omitted from the figure. Horizontal bars represent mean values. SI, Stimulation index. Journal of Allergy and Clinical Immunology 2005 115, 323-329DOI: (10.1016/j.jaci.2004.11.041) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 5 Api m [1/2] retains T-cell epitopes of Api m 1. Api m 1–specific T-cell clones (BuT 6.1 F10 and BuT 6.6 F4) and Api m 1–nonspecific T-cell clones (BuT 5.1 F12 and BuT 7.3 B4) were stimulated with equimolar amounts of Api m 1, Api m 2, and Api m [1/2] fusion protein for 48 hours. 3[H] thymidine incorporation was measured 12 hours after addition. Ag, Antigen. Journal of Allergy and Clinical Immunology 2005 115, 323-329DOI: (10.1016/j.jaci.2004.11.041) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 6 Api m [1/2] suppresses antibody development against native allergen. Mice (n=6) were pretreated subcutaneously with Api m [1/2] in saline or saline alone as control 14, 10, and 6 days before intraperitoneal immunization with Api m 1/AL(OH)3. Serum Api m 1–specific IgE, IgG1, and IgG2a were determined. ∗P < .001. Journal of Allergy and Clinical Immunology 2005 115, 323-329DOI: (10.1016/j.jaci.2004.11.041) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions