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

In Japan, standardization of allergens for therapeutics and diagnosis is very limited. Only one allergen (Cryptomeria japonica) extract was standardized. The standardization of two kinds of allergens for therapeutics (Cedar pollen and Dermatophagoides allergens) is now progressing. As for food allergens, the Japanese Ministry of Health Labour and Welfare (MHLW) made a decision for mandatory labeling of foods containing allergenic ingredients in 2001. Egg, milk, wheat, buckwheat and peanut, and most recently shrimp and crab require mandatory labeling. Standardization of food allergens for allergenic ingredient measurement has been advanced.

The new concept of immunotherapy with IVN201 against cat dander allergy combines two proprietary technology platforms: Intralymphatic immunotherapy (ILIT) with Modular-Antigen-Transportation (MAT) proteins. Intralymphatic immunotherapy (ILIT) is the injection of immunotherapeutics directly into the lymph node. Lymph nodes contain a high density of antigen presenting cells together with interacting T cells, which are necessary for allergen tolerance development. Therefore, this site-directed route of administration requires fewer injections of much smaller doses of the allergen than conventional administration routes to induce a highly effective, disease modifying immune response. ILIT was recently demonstrated in a clinical study to enhance safety and efficacy of immunotherapy and to reduce treatment time from 3 years to 8 weeks with only three injections, thereby significantly improving patient compliance. Patients subjectively perceived the intralymphatic injections less painful than a venous puncture. IVN201 is a functional fusion peptide which is a tailor-made recombinant allergen for ILIT with Fel d 1 as allergen module. It is designed to be rapidly taken up by antigen presenting cells in the lymph nodes and to improve the presentation of the allergen to the immune system. IVN201 was shown to induce allergen tolerance in a murine anaphylaxis model. Stimulation assays with basophil leukocytes isolated from allergic patients suggest an increased safety profile when compared to cat extract or recombinant Fel d 1. Therefore, MAT molecules are expected to be safer and more efficacious in inducing the desired immune response than recombinant allergens or allergen extracts in allergen immunotherapy when administered via the intralymphatic route.

Allergens are embedded into the protein universe as members of large families and superfamilies of related proteins which is a direct consequence of their shared evolution. The classification of allergens by protein families offers a valuable frame of reference that allows the design of experiments to study cross-reactivity and allergenic potency of proteins. Information on protein family membership also complements the current official IUIS allergen nomenclature. All presently known allergens belong to one of 140 (1.4%) of the 10,340 protein families currently described by version 23.0 of the Pfam database. This is indicative of a strong bias among allergens towards certain protein architectures that are able to induce an IgE response in an atopic immune system. However, even small variations in the structure of a protein alter its immunological characteristics. Various isoforms of the major birch pollen allergen Bet v 1 were shown to possess highly variant immunogenic and allergenic properties. Ber e 1 and SFA8, two 2S albumins, were revealed to display differential capacities to polarise an immune response. Such data will be exploited in the future for the design of allergy vaccines.

Background: Compared to conventional methods, infrared spectroscopy offers many potential uses in quality control of vaccine production. A major advantage is that the technique is non-invasive and non-destructive. In this study several possible uses of infrared spectroscopy in the control of allergy vaccines were investigated.

Methods: Near infrared spectroscopy (NIR) was applied to determine the aluminium content in aluminium hydroxide formulations, the particle size of aluminium hydroxide, the protein adsorption level on aluminium adjuvant and the moisture content of lyophilized vaccines. Mid infrared spectroscopy (IR) was used to investigate protein structural changes during adsorption and release from aluminium hydroxide and the stability of the complex.

Results: Based on the calibration models of NIR in different applications, it was demonstrated that NIR had great advantages for application in vaccine production. IR also showed advantages on structural analysis of adsorbed proteins.

Discussion: Infrared spectroscopy as a physical, non-invasive, non-destructive method should receive more attention in vaccine research and production.