Allergopharma GmbH and Co. KG

Reinbek, Germany

Allergopharma GmbH and Co. KG

Reinbek, Germany

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Himly M.,University of Salzburg | Nandy A.,Allergopharma GmbH and Co. KG | Kahlert H.,Allergopharma GmbH and Co. KG | Thilker M.,Allergopharma GmbH and Co. KG | And 7 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2016

Background The Biological Standardization Programme of the European Directorate for Quality of Medicines and Healthcare (EDQM) aims at the establishment of well-characterized reference standards based on recombinant allergens and validated assays for the quantification of major allergen content. The objective of this study was to examine the detailed physicochemical and immunological characterization of recombinant Phl p 5.0109, the second available allergen reference standard. Methods Recombinant Phl p 5.0109 PP5ar06007 was produced under GMP conditions and analyzed by an array of physicochemical and immunological methods for identity, quantity, homogeneity, and folding stability in bulk solution, as well as thermal denaturation, aggregation state, and biological activity when formulated for long-time storage. Results PP5ar06007 revealed as a highly homogeneous, monomeric, well-folded preparation of rPhl p 5.0109, as documented by mass spectrometry, SDS-PAGE, isoelectric focusing, size-exclusion chromatography with light scattering, circular dichroism, and infrared spectroscopy. Upon storage at +4°C, PP5ar06007 retained the monomeric state for at least 2 months. A protein quantity of 1.56 ± 0.03 mg/ml was determined by amino acid analysis in PP5ar06007, and its biological activity was shown to be comparable to natural Phl p 5 in terms of basophil activation and T-cell reactivity. Conclusions Recombinant Phl p 5.0109 PP5ar06007 was characterized extensively at the physicochemical and immunological level. It revealed to be a highly stable, monomeric, and immunologically equivalent of its natural counterpart. PP5ar06007 is now available as European Pharmacopoeia allergen reference standard for grass pollen products. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Ullrich D.,Otorhinolaryngological Medical Practice Day Surgery | Ullrich K.,Otorhinolaryngological Medical Practice Day Surgery | Mussler S.,Allergopharma GmbH and Co. KG | Thum-Oltmer S.,Allergopharma GmbH and Co. KG
European Annals of Allergy and Clinical Immunology | Year: 2015

Background. During subcutaneous immunotherapy (SCIT), injections should be separated from vaccinations against infectious diseases by at least 1 week, because it is assumed that adverse reactions can result from the additional activation of the immune system. Material and Methods. Data of a total of 875 individuals receiving SCIT and/or vaccination in one ENT-practice were included and analyzed retrospectively. 444 individuals had received vaccination against infectious diseases, 336 allergic patients received only SCIT. Moreover, 79 allergic patients had received vaccination and SCIT injections simultaneously on one day in different locations, while 16 patients inadvertently received SCIT injections within up to 4 days after vaccination. Some of the patients were observed for consecutive years receiving several vaccinations parallel to SCIT. Systemic reactions (SRs) during SCIT were classified according to the WAO (World Allergy Organization) grading. Results. Patients exclusively receiving vaccinations did not report any drug-related SR. One SR third grade and two SRs second grade occurred in 3 asthmatic patients exclusively receiving SCIT. The patients simultaneously receiving vaccination and SCIT did not have any SR. This was also the case for the subjects consecutively receiving parallel SCIT and vaccination for up to 5 years. Conclusion. The international guidelines for allergen-specific immunotherapy (SIT) recommend an intermission of at least one week between SCIT and the administration of vaccines. However, these findings demonstrate the possibility to shorten or abolish this interval without increasing the risk of SRs. © 2015, EDRA LSWR. All rights reserved.


Buters J.,Helmholtz Center Munich | Buters J.,Kuhne Foundation | Prank M.,Finnish Meteorological Institute | Sofiev M.,Finnish Meteorological Institute | And 23 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background Allergies to grass pollen are the number one cause of outdoor hay fever. The human immune system reacts with symptoms to allergen from pollen. Objective We investigated the natural variability in release of the major group 5 allergen from grass pollen across Europe. Methods Airborne pollen and allergens were simultaneously collected daily with a volumetric spore trap and a high-volume cascade impactor at 10 sites across Europe for 3 consecutive years. Group 5 allergen levels were determined with a Phl p 5-specific ELISA in 2 fractions of ambient air: particulate matter of greater than 10 μm in diameter and particulate matter greater than 2.5 μm and less than 10 μm in diameter. Mediator release by ambient air was determined in FcεRI-humanized basophils. The origin of pollen was modeled and condensed to pollen potency maps. Results On average, grass pollen released 2.3 pg of Phl p 5 per pollen. Allergen release per pollen (potency) varied substantially, ranging from less than 1 to 9 pg of Phl p 5 per pollen (5% to 95% percentile). The main variation was locally day to day. Average potency maps across Europe varied between years. Mediator release from basophilic granulocytes correlated better with allergen levels per cubic meter (r2 = 0.80, P <.001) than with pollen grains per cubic meter (r2 = 0.61, P <.001). In addition, pollen released different amounts of allergen in the non-pollen-bearing fraction of ambient air, depending on humidity. Conclusion Across Europe, the same amount of pollen released substantially different amounts of group 5 grass pollen allergen. This variation in allergen release is in addition to variations in pollen counts. Molecular aerobiology (ie, determining allergen in ambient air) might be a valuable addition to pollen counting. © 2015 American Academy of Allergy, Asthma & Immunology.


Devanaboyina S.C.,University of Graz | Devanaboyina S.C.,University of Texas Southwestern Medical Center | Cornelius C.,Medical University of Vienna | Lupinek C.,Medical University of Vienna | And 8 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

Background: Group 2 and 3 grass pollen allergens are major allergens with high allergenic activity and exhibit structural similarity with the C-terminal portion of major group 1 allergens. In this study, we aimed to determine the crystal structure of timothy grass pollen allergen, Phl p 3, and to study its IgE recognition and cross-reactivity with group 2 and group 1 allergens. Methods: The three-dimensional structure of Phl p 3 was solved by X-ray crystallography and compared with the structures of group 1 and 2 grass pollen allergens. Cross-reactivity was studied using a human monoclonal antibody which inhibits allergic patients' IgE binding and by IgE inhibition experiments with patients' sera. Conformational Phl p 3 IgE epitopes were predicted with the algorithm SPADE, and Phl p 3 variants containing single point mutations in the predicted IgE binding sites were produced to analyze allergic patients' IgE binding. Results: Phl p 3 is a globular β-sandwich protein showing structural similarity to Phl p 2 and the Phl p 1-C-terminal domain. Phl p 3 showed IgE cross-reactivity with group 2 allergens but not with group 1 allergens. SPADE identified two conformational IgE epitope-containing areas, of which one overlaps with the epitope defined by the monoclonal antibody. The mutation of arginine 68 to alanine completely abolished binding of the blocking antibody. This mutation and a mutation of D13 in the predicted second IgE epitope area also reduced allergic patients' IgE binding. Conclusion: Group 3 and group 2 grass pollen allergens are cross-reactive allergens containing conformational IgE epitopes. They lack relevant IgE cross-reactivity with group 1 allergens and therefore need to be included in diagnostic tests and allergen-specific treatments in addition to group 1 allergens. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Kanatani K.T.,Kyoto University | Slingsby B.T.,Kyoto University | Slingsby B.T.,Eisai Co. | Slingsby B.T.,University of Tokyo | And 5 more authors.
Allergology International | Year: 2013

Background: Symptom and medication scores are recommended to measure the primary outcome on allergies. The Allergy Control Score was proved to be a valid and reliable instrument to assess allergy severity in clinical trials and may be used in observational studies of respiratory allergic diseases in many countries. We translated the Allergy Control Score and adapted it for use in Japan. Methods: We translated the original English version into Japanese according to the Mapi approach to linguistic validation: conceptual definition, forward translation by two native Japanese speakers, reconciliation, backtranslation by an independent translator, review in consultation with original developer, and pilot testing on 12 patients of an allergy clinic and 3 volunteers with seasonal/ non-seasonal allergic rhinitis and/ or asthma. Results: Two of the ten back-translated items needed slight modifications and some words were revised. In the pilot test, the average time required to complete the questionnaire was 55 seconds for the section on symptoms and 25 seconds for the section on medication. All participants were able to self-complete the questionnaire. Conclusions: By applying the Mapi approach to linguistic validation, we ensured a close match between the Japanese and English versions of the Allergy Control Score. The Allergy Control Score Japanese version is accessible and acceptable to persons with respiratory allergic symptoms in Japan. © 2013 Japanese Society of Allergology.


Muller M.,Allergopharma GmbH and Co. KG | Reiss S.,Allergopharma GmbH and Co. KG | Schluter R.,Allergopharma GmbH and Co. KG | Mader U.,University of Greifswald | And 12 more authors.
Molecular Microbiology | Year: 2014

With about 25000 molecules per cell, Asp23 is one of the most abundant proteins in Staphylococcus aureus. Asp23 has been characterized as a protein that, following an alkaline shock, accumulates in the soluble protein fraction. Transcription of the asp23 gene is exclusively regulated by the alternative sigma factor σB, which controls the response of the bacterium to environmental stress. Sequence analysis identified Asp23 as a member of the widely distributed Pfam DUF322 family, precluding functional predictions based on its sequence. Using fluorescence microscopy we found that Asp23 colocalized with the cell membrane of Staphylococcus aureus. Since Asp23 has no recognizable transmembrane spanning domains, we initiated a search for proteins that link Asp23 to the cell membrane. We identified SAOUHSC_02443 as the Asp23 membrane anchor and have renamed it AmaP (Asp23 membrane anchoring protein). Deletion of the asp23 gene led to an upregulation of the cell wall stress response. In summary, we have identified Asp23 as a membrane-associated protein and we suggest a function for Asp23 in cell envelope homoeostasis. © 2014 John Wiley & Sons Ltd.


Egert-Schmidt A.-M.,Allergopharma GmbH and Co. KG | Kolbe J.-M.,Allergopharma GmbH and Co. KG | Mussler S.,Allergopharma GmbH and Co. KG | Thum-Oltmer S.,Allergopharma GmbH and Co. KG
Patient Preference and Adherence | Year: 2014

Background: Allergen immunotherapy (AIT) is the practice of administering gradually increasing quantities of an allergen extract to an allergic subject to ameliorate the symptoms associated with the subsequent exposure to the causative allergen. It is the only treatment that may alter the natural course of allergic diseases. According to AIT guidelines and summary of product characteristics (SmPCs), the treatment should be carried out for at least 3 years. It is controversially discussed whether subcutaneous or sublingual administration routes cause higher patients’ compliance. Methods: German sales data for different preparations of the allergen manufacturer Allergopharma GmbH & Co. KG were retrospectively evaluated for 5 consecutive years, based on prescriptions per patient: pollen sublingual immunotherapy (SLIT) and high-dose hypoallergenic (allergoid) or unmodified depot pollen and mite preparations for subcutaneous immunotherapy (SCIT). To identify patients’ compliance, “completed treatment years” were determined. A completed treatment year was defined by the required number of prescribed allergen preparations according to the recommended dosage scheme given in the respective SmPCs. Results: Prescription data of 85,241 patients receiving pollen or mite SCIT and 706 patients receiving pollen SLIT were included in this analysis. Patients’ compliance for at least 3 treatment years with high-dose hypoallergenic pollen SCIT was higher when administered perennially (60%) compared to preseasonally (27%). Prescriptions for at least 3 years were received from 42% of patients with pollen SCIT and from 45% of patients with mite SCIT. Compliance with SLIT was lowest with only 16% of patients receiving prescriptions for at least 3 treatment years. Children and adolescents were more compliant than adults, independent of whether they received SLIT or SCIT. Conclusion: In general, patients’ compliance with SCIT using high-dose hypoallergenic or unmodified depot preparations was higher than with pollen SLIT. Perennial application of SCIT seems to increase compliance in comparison to the preseasonal application. Children and adolescents were most compliant, independent of the preparation applied. © 2014 Egert-Schmidt et al.


Hafner D.,Allergopharma GmbH and Co. KG | Godicke V.,Allergopharma GmbH and Co. KG | Narkus A.,Allergopharma GmbH and Co. KG
Clinical and Translational Allergy | Year: 2014

Background: A set of standard clinical chemistry and hematology parameters are usually measured during clinical studies. The major outcome of these standard tests is to control that the drug investigated does not lead to pathophysiological changes in respective organs or blood. In some cases based on scientific rationale such tests may not be needed. In this paper we report on a standard set of clinical chemistry and hematology laboratory parameters measured before and after treatment in three different immunotherapy studies, representing different routes of administration and different formulations. Methods: Thirteen hematological laboratory parameters and eight clinical chemistry parameters were evaluated from three double-blind, placebo-controlled, randomized, multi-centre, phase III studies. The three studies include one with sublingual immunotherapy (n = 185), one subcutaneous immunotherapy trial with an aluminium hydroxide-adsorbed recombinant hypoallergenic Bet v1-FV (n = 211) and one with pre-seasonal subcutaneous immunotherapy with a 6-grass pollen allergoid (n = 154). Results: Allergen specific immunotherapy with both administration forms and formulations respectively did not show any influence on any of the 21 laboratory parameters analyzed. Few patients had a change in laboratory parameters from within normal range at baseline to either below or above at end-of-treatment. No differences between active and placebo were seen with respect to number of patients with such a change. Conclusions: This study with different preparations and routes of application indicates that the value of repeated measurements of standard clinical chemistry and hematology parameters during allergen immunotherapy should be discussed further. © 2014 Häfner et al.

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