Use of a genetic cholera toxin B subunit/allergen fusion molecule as mucosal delivery system with immunosuppressive activity against Th2 immune responses.
ABSTRACT Induction of peripheral tolerance can be facilitated when the antigen is linked to the B subunit of cholera toxin (CTB), an efficient mucosal carrier. In the present study, a genetic fusion molecule of Bet v 1 and CTB was produced to test whether mucosal application of this construct would lead to suppression of Th2 responses. Intranasal pretreatment of BALB/c mice with rCTB-Bet v 1 prior to allergic sensitisation with the allergen significantly decreased IgE but markedly increased allergen-specific IgG2a levels in sera as well as IFN-gamma production of splenocytes. This Th1 shift was supported by an increased T-bet/GATA3 mRNA ratio. IL-5 production within the airways was suppressed after the pretreatment with rCTB-Bet v 1, while local allergen-specific IgA antibodies were markedly enhanced by pretreatment with the construct. Upregulation of Foxp3, IL-10 and TGF-beta mRNA expression was detected in splenocytes after pretreatment with unconjugated allergen but not with the fusion molecule, indicating that antigen conjugation to a mucosal carrier modifies the immunomodulating properties of an antigen/allergen.
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ABSTRACT: It has been suggested that a reduced or changed pattern of exposure to certain microorganisms has led to an unbalanced regulation of our im-mune system with consequently increased development of inflamma-tory diseases, such as allergic or autoimmune disorders. Studies on the basis of this so called "hygiene hypothesis" have concentrated on identifying microorganisms that may have the potential to re-establish a regulatory network important to prevent or counteract immune overreactions to innocuous antigens leading to immunopathology. Using mouse models of type I allergy/asthma we tested several ap-proaches to prevent or treat allergic immune responses, either by the use of mucosal adjuvants, the application of certain lactic acid bacteria as antigen delivery systems or by parasite inoculation. The goal of our research is to exploit the underlying mechanisms of immune modula-tion and to identify some of the microbial components with immuno-modulatory properties, which may serve as novel treatment tools against inflammatory disorders, including allergic diseases.
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ABSTRACT: Specific immunotherapy (IT) represents the only potentially curative therapeutic intervention of allergic diseases capable of suppressing allergy-associated symptoms not only during treatment, but also after its cessation. Presently, IT is performed with allergen extracts, which represent a heterogeneous mixture of allergenic, as well as nonallergenic, compounds of a given allergen source. To overcome many of the problems associated with extract-based IT, strategies based on the use of recombinant allergens or derivatives thereof have been developed. This review focuses on recombinant technologies to produce allergy therapeuticals, especially for allergies caused by tree, grass and weed pollen, as they are among the most prevalent allergic disorders affecting the population of industrialized societies. The reduction of IgE-binding of recombinant allergen derivatives appears to be mandatory to increase the safety profile of vaccine candidates. Moreover, increased immunogenicity is expected to reduce the dosage regimes of the presently cumbersome treatment. In this regard, it has been convincingly demonstrated in animal models that hypoallergenic molecules can be engineered to harbor inherent antiallergenic immunologic properties. Thus, strategies to modulate the allergenic and immunogenic properties of recombinant allergens will be discussed in detail. In recent years, several successful clinical studies using recombinant wild-type or hypoallergens as active ingredients have been published and, currently, novel treatment forms with higher safety and efficacy profiles are under investigation in clinical trials. These recent developments are summarized and discussed.Immunotherapy 12/2013; 5(12):1323-1338. DOI:10.2217/imt.13.114 · 2.44 Impact Factor
Article: Kan typ I-allergier botas