Arbeiten aus dem Paul-Ehrlich-Institut (Bundesinstitut fur Impfstoffe und biomedizinische Arzneimittel) Langen/Hessen最新文献

Novel therapies that interfere specifically with immunological mechanisms underlying allergen-induced pathology are currently in clinical evaluation. Among these is anti-IgE, which directly targets IgE serum antibodies, thus inhibiting the central mechanism of immediate type hypersensitivity reactions. Application of anti-IgE antibodies effectively reduces IgE serum levels regardless of allergen specificity. It has been successfully tested in patients with allergic rhinitis, asthma and food allergy, showing significant efficacy in reducing symptom scores and use of rescue medications. Anti-IgE therapy is limited by high costs and the requirements for permanent or every-season treatment. The advantage of specific immune therapy (SIT) is the potential to alter the course of the disease, which has been demonstrated in patients with allergic rhinitis, insect venom allergy and, to a lesser degree, with asthma. The broader application of SIT is restricted by sometimes life-threatening side-effects. Here, we summarize the results of clinical trials investigating the effects of combination therapy with anti-IgE and SIT in patients with rhinitis and asthma. These studies show that combination of anti-IgE plus SIT may be beneficial for the treatment of allergic diseases by improving efficacy and limiting side effects.

A variety of positive outcomes can be realized from validation and risk management activities (see Table 4). They are dependent on the participation of multiple functional groups including the quality unit, regulatory and legal affairs, engineering and production operations, research and development, and sales and marketing. Quality risk management is receiving increased attention in the area of public health, pharmacovigilance, and pharmaceutical manufacturing. Recent examples of its regulatory use in our industry include the assessment of the potential risks of transmissible spongiform encephalopathies (TSE) agents through contaminated products], the risks of precipitates in allergenic extracts, and the revision of the potency limits for standardized dust mite and grass allergen vaccines. Its application to allergen source material process validation activities allowed for a practical strategy, especially in a complex manufacturing environment involving hundreds of products with multiple intended uses. In addition, the use of tools such as FMEA was useful in evaluating proposed changes made to manufacturing procedures and product specifications, new regulatory actions, and customer feedback or complaints. The success of such a quality assurance programs will ultimately be reflected in the elimination or reduction of product failures, improvement in the detection and prediction of potential product failures, and increased confidence in product quality.

So far it has not been possible to measure the amount of major allergens in the complexes after chemical modification. Furthermore, the presence of minor allergens remained obscure, unless antibodies were successfully generated by animal immunization with allergoids and shown to be reactive with purified natural or recombinant allergens in immunological assays. Thus, we adapted and employed a set of physicochemical methods with the aim of elucidating the molecular size and allergen composition of allergoids. Using online-HPSEC light scattering and DLS, it was shown that two thirds of depigmented allergoid prepared from birch pollen extracts adopted a MW between 1000 and 2000 kDa. The question of reproducibility of the polymerization reaction was addressed by investigating four batches of P. pratense allergoid. Three out of the four batches contained 73 to 77% of polymerized molecules in the above-mentioned range of molecular sizes. One batch showed a significantly higher content of molecules with a MW exceeding 2 MDa. Analysis of allergen composition in B. alba allergoids revealed the presence of all relevant Bet v 1 isoforms and minor allergens except for Bet v 3 and Bet v 4, which was in good agreement with the allergens detected in the native extracts. It should be noted that Bet v 3 has not been detected at the protein level before. Similarly, good agreement in allergen composition between allergoid and native extract was also found for D. pteronyssinus. Presently, the European Directorate for Quality of Medicines and Healthcare (EDQM) is committed to the application of the 3R principles (i. e. replace, reduce, refine the use of animals) for the quality control of medicines wherever possible. This is reflected by the regular review of the monographs of the European Pharmacopoeia and the introduction of alternative tests. For instance, recently it was decided to replace the rabbit pyrogen test by an in vitro test. Furthermore, through the Biological Standardisation Programme the EDQM develops, validates, and establishes alternative test methods in the field of quality control of biologicals (personal communication with Karl-Heinz Buchheit, EDQM). Therefore, the approach presented here for the characterization of allergoids relying on physicochemical methods shall also serve the growing needs for alternative methods to animal testing.