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Verena Niederberger - One of the best experts on this subject based on the ideXlab platform.
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recombinant allergy vaccines based on allergen derived b cell epitopes
Immunology Letters, 2017Co-Authors: Rudolf Valenta, Raffaela Campana, Verena NiederbergerAbstract:Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensitivity disease. It affects more than 25% of the population. In IgE-sensitized subjects, allergen encounter can causes a variety of symptoms ranging from hayfever (allergic rhinoconjunctivitis) to asthma, skin inflammation, food allergy and severe life-threatening anaphylactic shock. Allergen-specific immunotherapy (AIT) is based on vaccination with the disease-causing Allergens. AIT is an extremely effective, causative and disease-modifying treatment. However, administration of natural Allergens can cause severe side effects and the quality of natural allergen extracts limits its application. Research in the field of molecular allergen characterization has allowed deciphering the molecular structures of the disease-causing Allergens and it has become possible to engineer novel molecular allergy vaccines which precisely target the mechanisms of the allergic immune response and even appear suitable for prophylactic allergy vaccination. Here we discuss recombinant allergy vaccines which are based on allergen-derived B cell epitopes regarding their molecular and immunological properties and review the results obtained in clinical studies with this new type of allergy vaccines.
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recombinant allergen based provocation testing
Methods, 2014Co-Authors: Verena Niederberger, Julia Eckldorna, G PauliAbstract:Over the last 25 years, recombinant Allergens from all important allergen sources have been cloned and are now available as recombinant proteins. These molecules can be produced in practically unlimited amounts without biological or batch-to-batch variability. It has been shown in provocation tests that recombinant Allergens have similar clinical effects as their natural counterparts. With the help of these tools it is possible to reveal the precise reactivity profiles of patients and to uncover and differentiate cross-reactivity from genuine sensitization to an allergen source. Although it has been shown some time ago that it would be possible to replace crude allergen extracts with recombinant Allergens for skin prick testing, and even though the use of allergen components can improve routine diagnosis, these tools are still not available for clinical routine applications. The use of provocation tests is a crucial step in the development of new, hypoallergenic vaccines for therapy of allergic disease. Here we describe important provocation methods (skin prick test, intradermal test, atopy patch test, nasal provocation, colonoscopic provocation test) and give an overview of the clinical provocation studies which have been performed with recombinant Allergens so far.
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the allergen profile of ash fraxinus excelsior pollen cross reactivity with Allergens from various plant species
Clinical & Experimental Allergy, 2002Co-Authors: Verena Niederberger, Susanne Spitzauer, Rudolf Valenta, A Purohit, J P Oster, G PauliAbstract:Summary Background Ash, a wind-pollinated tree belonging to the family Oleaceae, is distributed world-wide and has been suggested as a potent allergen source in spring time. Objective The aim of this study was to determine the profile of allergen components in ash pollen in order to refine diagnosis and therapy for patients with sensitivity to ash pollen Methods The IgE reactivity profile of 40 ash pollen-allergic patients was determined by immunoblotting. Antibodies raised to purified pollen Allergens from tree and grass pollens were used to identify cross-reactive structures in ash pollen extract. IgE immunoblot inhibition studies were performed with recombinant and natural pollen Allergens to characterize ash pollen Allergens and to determine the degree of cross-reactivity between pollen Allergens from ash, olive, birch, grasses and weeds. Results The allergen profile of ash pollen comprises Fra e 1, a major allergen related to the major olive allergen, Ole e 1, and to group 11 grass pollen Allergens, the panallergen profilin, a two EF-hand calcium-binding protein, a pectinesterase-like molecule and an allergen sharing epitopes with group 4 grass pollen Allergens. Thus, the relevant Allergens of ash are primarily Allergens that share epitopes with pollen Allergens from other tree, grass and weed species. Conclusions Allergic symptoms to ash pollen can be the consequence of sensitization to cross-reactive Allergens from other sources. The fact that ash pollen-allergic patients can be discriminated on the basis of their specific IgE reactivity profile to highly or moderately cross-reactive Allergens has implications for the selection of appropriate forms of treatment.
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skin test results but not serology reflect immediate type respiratory sensitivity a study performed with recombinant allergen molecules
Journal of Investigative Dermatology, 2001Co-Authors: Verena Niederberger, Susanne Spitzauer, Petra Stubner, Klaus Ehrenberger, Friedrich HorakAbstract:The diagnosis of type I allergy, an IgE-antibody-mediated hypersensitivity disease affecting more than 25% of the population, is based on the measurement of allergen-specific serum IgE levels and provocation testing. Whether the determination of allergen-specific serum IgE levels can replace in vivo provocation testing for allergy diagnosis is a controversial issue. We used purified recombinant timothy grass and birch pollen Allergens to compare by skin prick and nasal provocation testing as well as by serology in vivo sensitivity with antibody-binding capacity in 24 pollen allergic patients and eight control individuals. Results from biologic tests were correlated with each other and with allergen-specific IgE and IgG 1-4 levels. IgE-reactive Allergens induced immediate skin and nasal reactions, but the intensity of the allergic tissue reactions was not correlated with either the levels of allergen-specific IgE or the levels of allergen-specific IgG antibodies. Less frequently detected Allergens with low IgE-binding capacity were able to induce strong allergic reactions comparable to those caused by major Allergens with high IgE-binding capacity. In contrast, skin test and nasal provocation results were significantly correlated ( r = 0.63, p
Anna Pomés - One of the best experts on this subject based on the ideXlab platform.
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ige and t cell reactivity to a comprehensive panel of cockroach Allergens in relation to disease
Frontiers in Immunology, 2021Co-Authors: Anna Pomés, Veronique Schulten, Jill Glesner, Ricardo Da Silva Antunes, Aaron Sutherland, Leonard B Bacharier, Avraham Beigelman, Paula J BusseAbstract:IgE sensitization to cockroach Allergens is associated with development of allergic diseases, such as asthma. To understand the relevance of different cockroach Allergens for diagnosis and immunotherapy, a comprehensive analysis of IgE antibody levels and T cell reactivity to an expanded set of cockroach Allergens and their relationship to disease was performed in a cohort of USA cockroach sensitized patients. IgE antibody levels to recombinant chitinase and hemocyanin were measured for 23 subjects by custom-made ImmunoCAPs and compared with IgE levels to eight cockroach Allergens we previously reported for the same cohort. Ex vivo T cell activation (Ox40/PDL-1 expression) of PBMCs stimulated with peptide pools derived from 11 German cockroach proteins, including nine official cockroach Allergens, plus chitinase and vitellogenin, was determined by flow cytometry. IgE prevalences to chitinase (17%) and hemocyanin (44%) were comparable to values for the other eight Allergens that we previously reported (21-57%). Hemocyanin (Bla g 3), was a major allergen (one to which more than 50% of patients with an allergy to its source react) for a sub-group of 15 highly cockroach-sensitized subjects (IgE > 3.5 kUA/L: 53%). Chitinase was officially named as new allergen Bla g 12. Cockroach-specific IgE levels in plasma showed excellent correlation with the sum of 10 allergen-specific IgE (r = 0.94, p < 0.001). T cell reactivity to 11 proteins was highly variable among subjects, the highest being for vitellogenin, followed by Bla g 3. The main finding was that cockroach allergen-specific IgE and T cell reactivity patterns were unique per subject, and lacked immunodominant Allergens and correlation with clinical phenotype/disease severity in the studied cohort. Knowing the subject-specific B/T cell reactivity profiles to a comprehensive panel of cockroach Allergens will contribute to diagnosis of cockroach allergy and will be important for planning and assessing allergen immunotherapy outcomes, according to the allergen content in therapeutic cockroach extracts.
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cockroach allergen component analysis of children with or without asthma and rhinitis in an inner city birth cohort
The Journal of Allergy and Clinical Immunology, 2019Co-Authors: Anna Pomés, Meyer Kattan, Robert A Wood, George T Oconnor, Jill Glesner, Leonard B Bacharier, Agustin Calatroni, Cindy M Visness, Lisa M Wheatley, James E GernAbstract:Background Cockroach is one of the most important sources of indoor Allergens and can lead to IgE sensitization and development of rhinitis and asthma. Objective We sought to perform a cockroach allergen component analysis to determine the Allergens and antibody levels and patterns of sensitization associated with asthma and rhinitis. Methods Antibody (IgE, IgG, and IgG4) levels to total cockroach and 8 cockroach Allergens were determined in 2 groups of cockroach-sensitized 10-year-old children with (n = 19) or without (n = 28) asthma and rhinitis. Allergen-specific antibody levels were measured in streptavidin ImmunoCAPs loaded with each of the recombinant Allergens from groups 1, 2, 4, 5, 6, 7, 9, and 11, and total cockroach-specific IgE levels were measured with the i6 ImmunoCAP. Results IgE antibody levels to cockroach Allergens and extract, but not IgG or IgG4 antibody levels, differed between subjects with and without asthma and rhinitis. Specifically, recognition of more cockroach Allergens with higher allergen-specific IgE levels was associated with disease. Variable patterns of sensitization with no immunodominant Allergens were found in both groups. There was a good correlation between the sum of allergen-specific IgE and total cockroach IgE levels (r = 0.86, P Conclusions Component analysis of 8 cockroach Allergens revealed significant differences in IgE reactivity associated with the presence of asthma and rhinitis. Allergen-specific IgE titers and sensitization profiles were associated with asthma and rhinitis.
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recombinant Allergens for diagnosis and therapy of allergic disease
The Journal of Allergy and Clinical Immunology, 2000Co-Authors: Martin D Chapman, Lisa D Vailes, Alisa M Smith, Karla L Arruda, V Dhanaraj, Anna PomésAbstract:Many of the problems associated with using natural allergenic products for allergy diagnosis and treatment can be overcome with use of genetically engineered recombinant Allergens. Over the past 10 years, the most important Allergens from mites, pollens, animal dander, insects, and foods have been cloned, sequenced, and expressed. In many cases the three-dimensional allergen structure has been determined and B-cell and T-cell epitopes have been mapped. These studies show that Allergens have diverse biologic functions (they may be enzymes, enzyme inhibitors, lipocalins, or structural proteins) and that as a rule the allergen function is unrelated to its ability to cause IgE antibody responses. High-level expression systems have been developed to produce recombinant Allergens in bacteria, yeast, or insect cells. Recombinant Allergens show comparable IgE antibody binding to their natural counterparts (where available) and show excellent reactivity on skin testing and in in vitro diagnostic tests. Cocktails of recombinant Allergens can be formulated with predetermined and uniform allergen levels, which could replace natural Allergens and result in the development of innovative, patient-based tests for allergy diagnosis. Recombinant Allergens also offer the exciting possibility of developing new forms of allergen immunotherapy, including the use of hypoAllergens, Allergens coupled to IgE suppressive adjuvants, and peptide-based therapies. The production of recombinant Allergens as defined molecular entities makes it feasible to consider the possibility of developing prophylactic allergen vaccines. The introduction of recombinant Allergens in research and in clinical trials should lead to significant improvements in allergy diagnosis and treatment.
Leonard B Bacharier - One of the best experts on this subject based on the ideXlab platform.
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ige and t cell reactivity to a comprehensive panel of cockroach Allergens in relation to disease
Frontiers in Immunology, 2021Co-Authors: Anna Pomés, Veronique Schulten, Jill Glesner, Ricardo Da Silva Antunes, Aaron Sutherland, Leonard B Bacharier, Avraham Beigelman, Paula J BusseAbstract:IgE sensitization to cockroach Allergens is associated with development of allergic diseases, such as asthma. To understand the relevance of different cockroach Allergens for diagnosis and immunotherapy, a comprehensive analysis of IgE antibody levels and T cell reactivity to an expanded set of cockroach Allergens and their relationship to disease was performed in a cohort of USA cockroach sensitized patients. IgE antibody levels to recombinant chitinase and hemocyanin were measured for 23 subjects by custom-made ImmunoCAPs and compared with IgE levels to eight cockroach Allergens we previously reported for the same cohort. Ex vivo T cell activation (Ox40/PDL-1 expression) of PBMCs stimulated with peptide pools derived from 11 German cockroach proteins, including nine official cockroach Allergens, plus chitinase and vitellogenin, was determined by flow cytometry. IgE prevalences to chitinase (17%) and hemocyanin (44%) were comparable to values for the other eight Allergens that we previously reported (21-57%). Hemocyanin (Bla g 3), was a major allergen (one to which more than 50% of patients with an allergy to its source react) for a sub-group of 15 highly cockroach-sensitized subjects (IgE > 3.5 kUA/L: 53%). Chitinase was officially named as new allergen Bla g 12. Cockroach-specific IgE levels in plasma showed excellent correlation with the sum of 10 allergen-specific IgE (r = 0.94, p < 0.001). T cell reactivity to 11 proteins was highly variable among subjects, the highest being for vitellogenin, followed by Bla g 3. The main finding was that cockroach allergen-specific IgE and T cell reactivity patterns were unique per subject, and lacked immunodominant Allergens and correlation with clinical phenotype/disease severity in the studied cohort. Knowing the subject-specific B/T cell reactivity profiles to a comprehensive panel of cockroach Allergens will contribute to diagnosis of cockroach allergy and will be important for planning and assessing allergen immunotherapy outcomes, according to the allergen content in therapeutic cockroach extracts.
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cockroach allergen component analysis of children with or without asthma and rhinitis in an inner city birth cohort
The Journal of Allergy and Clinical Immunology, 2019Co-Authors: Anna Pomés, Meyer Kattan, Robert A Wood, George T Oconnor, Jill Glesner, Leonard B Bacharier, Agustin Calatroni, Cindy M Visness, Lisa M Wheatley, James E GernAbstract:Background Cockroach is one of the most important sources of indoor Allergens and can lead to IgE sensitization and development of rhinitis and asthma. Objective We sought to perform a cockroach allergen component analysis to determine the Allergens and antibody levels and patterns of sensitization associated with asthma and rhinitis. Methods Antibody (IgE, IgG, and IgG4) levels to total cockroach and 8 cockroach Allergens were determined in 2 groups of cockroach-sensitized 10-year-old children with (n = 19) or without (n = 28) asthma and rhinitis. Allergen-specific antibody levels were measured in streptavidin ImmunoCAPs loaded with each of the recombinant Allergens from groups 1, 2, 4, 5, 6, 7, 9, and 11, and total cockroach-specific IgE levels were measured with the i6 ImmunoCAP. Results IgE antibody levels to cockroach Allergens and extract, but not IgG or IgG4 antibody levels, differed between subjects with and without asthma and rhinitis. Specifically, recognition of more cockroach Allergens with higher allergen-specific IgE levels was associated with disease. Variable patterns of sensitization with no immunodominant Allergens were found in both groups. There was a good correlation between the sum of allergen-specific IgE and total cockroach IgE levels (r = 0.86, P Conclusions Component analysis of 8 cockroach Allergens revealed significant differences in IgE reactivity associated with the presence of asthma and rhinitis. Allergen-specific IgE titers and sensitization profiles were associated with asthma and rhinitis.
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allergen content in german cockroach extracts and sensitization profiles to a new expanded set of cockroach Allergens determine in vitro extract potency for ige reactivity
The Journal of Allergy and Clinical Immunology, 2019Co-Authors: Jill Glesner, Coby Schal, Stephanie Filep, Lisa D Vailes, Sabina Wunschmann, Giovanni Birrueta, April Frazier, Kyoung Yong Jeong, Leonard B BacharierAbstract:Background Cockroach Allergens are an important cause of IgE-mediated sensitization in inner-city asthmatic patients. However, cockroach extracts used for diagnosis and immunotherapy are not standardized. Objective We sought to determine the allergen content of nonstandardized German cockroach extracts and the levels of sensitization to an expanded set of cockroach Allergens as determinants of in vitro extract potency for IgE reactivity. Methods Twelve German cockroach extracts were compared for allergen content and potency of IgE reactivity. Bla g 1, Bla g 2, and Bla g 5 were measured by using immunoassays. IgE antibody levels to 8 purified recombinant Allergens from groups 1, 2, 4, 5, 6, 7, 9, and 11 were measured by using ImmunoCAP. IgE antibody binding inhibition assays were performed to assess extract in vitro potencies (concentration inhibiting 30% of the total IgE antibody-binding inhibition) relative to an arbitrarily selected reference extract in 5 patients with cockroach allergy. Results Allergen levels were highly variable. Three new major Allergens (groups 6, 9, and 11), were identified among highly cockroach-sensitized subjects (CAP class ≥ 3). Sensitization profiles were unique per subject without immunodominant Allergens. The sum of IgE to 8 allergen components showed a good correlation with cockroach-specific IgE levels (r = 0.88, P Conclusions The in vitro potency of German cockroach extracts for IgE reactivity depends on allergen content and allergen-specific IgE titers of patients with cockroach allergy. These factors are relevant for selection of potent extracts to be used for immunotherapy and for the design and interpretation of data from immunotherapy trials.
G Pauli - One of the best experts on this subject based on the ideXlab platform.
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recombinant allergen based provocation testing
Methods, 2014Co-Authors: Verena Niederberger, Julia Eckldorna, G PauliAbstract:Over the last 25 years, recombinant Allergens from all important allergen sources have been cloned and are now available as recombinant proteins. These molecules can be produced in practically unlimited amounts without biological or batch-to-batch variability. It has been shown in provocation tests that recombinant Allergens have similar clinical effects as their natural counterparts. With the help of these tools it is possible to reveal the precise reactivity profiles of patients and to uncover and differentiate cross-reactivity from genuine sensitization to an allergen source. Although it has been shown some time ago that it would be possible to replace crude allergen extracts with recombinant Allergens for skin prick testing, and even though the use of allergen components can improve routine diagnosis, these tools are still not available for clinical routine applications. The use of provocation tests is a crucial step in the development of new, hypoallergenic vaccines for therapy of allergic disease. Here we describe important provocation methods (skin prick test, intradermal test, atopy patch test, nasal provocation, colonoscopic provocation test) and give an overview of the clinical provocation studies which have been performed with recombinant Allergens so far.
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the allergen profile of ash fraxinus excelsior pollen cross reactivity with Allergens from various plant species
Clinical & Experimental Allergy, 2002Co-Authors: Verena Niederberger, Susanne Spitzauer, Rudolf Valenta, A Purohit, J P Oster, G PauliAbstract:Summary Background Ash, a wind-pollinated tree belonging to the family Oleaceae, is distributed world-wide and has been suggested as a potent allergen source in spring time. Objective The aim of this study was to determine the profile of allergen components in ash pollen in order to refine diagnosis and therapy for patients with sensitivity to ash pollen Methods The IgE reactivity profile of 40 ash pollen-allergic patients was determined by immunoblotting. Antibodies raised to purified pollen Allergens from tree and grass pollens were used to identify cross-reactive structures in ash pollen extract. IgE immunoblot inhibition studies were performed with recombinant and natural pollen Allergens to characterize ash pollen Allergens and to determine the degree of cross-reactivity between pollen Allergens from ash, olive, birch, grasses and weeds. Results The allergen profile of ash pollen comprises Fra e 1, a major allergen related to the major olive allergen, Ole e 1, and to group 11 grass pollen Allergens, the panallergen profilin, a two EF-hand calcium-binding protein, a pectinesterase-like molecule and an allergen sharing epitopes with group 4 grass pollen Allergens. Thus, the relevant Allergens of ash are primarily Allergens that share epitopes with pollen Allergens from other tree, grass and weed species. Conclusions Allergic symptoms to ash pollen can be the consequence of sensitization to cross-reactive Allergens from other sources. The fact that ash pollen-allergic patients can be discriminated on the basis of their specific IgE reactivity profile to highly or moderately cross-reactive Allergens has implications for the selection of appropriate forms of treatment.
Peter Valent - One of the best experts on this subject based on the ideXlab platform.
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Molecular Evolution of Hypoallergenic Hybrid Proteins for Vaccination against Grass Pollen Allergy
Journal of Immunology, 2015Co-Authors: Birgit Linhart, Margarete Focke-tejkl, Milena Weber, Angela Neubauer, Meena Narayanan, Hannes Mayrhofer, Katharina Blatt, Christian Lupinek, Peter ValentAbstract:More than 10% of the population in Europe and North America suffer from IgE-associated allergy to grass pollen. In this article, we describe the development of a vaccine for grass pollen allergen-specific immunotherapy based on two recombinant hypoallergenic mosaic molecules, designated P and Q, which were constructed out of elements derived from the four major timothy grass pollen Allergens: Phl p 1, Phl p 2, Phl p 5, and Phl p 6. Seventeen recombinant mosaic molecules were expressed and purified in Escherichia coli using synthetic genes, characterized regarding biochemical properties, structural fold, and IgE reactivity. We found that depending on the arrangement of allergen fragments, mosaic molecules with strongly varying IgE reactivity were obtained. Based on an extensive screening with sera and basophils from allergic patients, two hypoallergenic mosaic molecules, P and Q, incorporating the primary sequence elements of the four grass pollen Allergens were identified. As shown by lymphoproliferation experiments, they contained allergen-specific T cell epitopes required for tolerance induction, and upon immunization of animals induced higher allergen-specific IgG Abs than the wild-type Allergens and a registered monophosphoryl lipid A–adjuvanted vaccine based on natural grass pollen allergen extract. Moreover, IgG Abs induced by immunization with P and Q inhibited the binding of patients’ IgE to natural Allergens from five grasses better than IgG induced with the wild-type Allergens or an extract-based vaccine. Our results suggest that vaccines based on the hypoallergenic grass pollen mosaics can be used for immunotherapy of grass pollen allergy.
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disruption of allergenic activity of the major grass pollen allergen phl p 2 by reassembly as a mosaic protein
Journal of Immunology, 2008Co-Authors: Nadine Mothesluksch, Birgit Linhart, Peter Valent, Sabine Stumvoll, M Focke, Marietherese Krauth, Alexander W Hauswirth, Petra Verdino, Tea Pavkov, Walter KellerAbstract:The recognition of conformational epitopes on respiratory Allergens by IgE Abs is a key event in allergic inflammation. We report a molecular strategy for the conversion of Allergens into vaccines with reduced allergenic activity, which is based on the reassembly of non-IgE-reactive fragments in the form of mosaic proteins. This evolution process is exemplified for timothy grass pollen-derived Phl p 2, a major allergen for more than 200 million allergic patients. In a first step, the allergen was disrupted into peptide fragments lacking IgE reactivity. cDNAs coding for these peptides were reassembled in altered order and expressed as a recombinant mosaic molecule. The mosaic molecule had lost the three-dimensional structure, the IgE reactivity, and allergenic activity of the wild-type allergen, but it induced high levels of allergen-specific IgG Abs upon immunization. These IgG Abs crossreacted with group 2 Allergens from other grass species and inhibited allergic patients' IgE binding to the wild-type allergen. The mosaic strategy is a general strategy for the reduction of allergenic activity of protein Allergens and can be used to convert harmful Allergens into safe vaccines.
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immunization with purified natural and recombinant Allergens induces mouse igg1 antibodies that recognize similar epitopes as human ige and inhibit the human ige allergen interaction and allergen induced basophil degranulation
Journal of Immunology, 1998Co-Authors: Susanne Vrtala, Susanne Spitzauer, Tanja Ball, Budhi Pandjaitan, Cenk Suphioglu, Bruce Knox, Wolfgang R Sperr, Peter ValentAbstract:Molecular characterization of Allergens by recombinant DNA technology has made rapid progress in the recent few years. In the present study we immunized mice with aluminum hydroxide-adsorbed purified recombinant major timothy grass pollen Allergens (rPhl p 1, rPhl p 2, rPhl p 5), dog albumin, a major animal dander allergen, and proteins with low (β-lactoglobulin) or no (ribulose diphosphate carboxylase) allergenic potential in humans. Allergens that bind high levels of IgE in humans (Phl p 1, Phl p 5, dog albumin) induced high IgE and IgG1 levels in mice, whereas proteins with little or no allergenic activity in humans failed to induce significant IgE and IgG1 levels in mice. Continuous immunization for a period of 27 wk resulted in the production of mouse IgG1 Abs that recognized recombinant allergen fragments/epitopes defined by IgE Abs of allergic patients. As a consequence, allergen-specific mouse Abs strongly inhibited human IgE binding to the Allergens and suppressed the allergen-induced histamine release from human basophils. In summary, our data indicate that 1) the allergenic potency of a protein may be related to its overall immunogenicity and 2) prolonged immunization with single purified recombinant Allergens induces protective IgG Abs. The presented experimental in vivo/in vitro system allows the evaluation of Ag preparations (e.g., recombinant Allergens) to be used for immunotherapy in humans.