Abstract
Peptide immunotherapy using T-cell epitopes is expected to be an effective treatment for allergic diseases such as Japanese cedar (Cryptomeria japonica; Cj) pollinosis. To develop a treatment for pollen allergy by inducing oral tolerance, we generated genetically manipulated (GM) chickens by retroviral gene transduction, to produce a fusion protein of chicken egg white lysozyme and a peptide derived from seven dominant human T-cell epitopes of Japanese cedar pollen allergens (cLys-7crp). The transgene sequence was detected in all chickens transduced with the retroviral vector. Transduction efficiency in blood cells correlated to transgene expression. Western blot analysis revealed that cLys-7crp was expressed in the egg white of GM hens. Mice induced to develop allergic rhinitis by Cj pollinosis were fed with cLys-7crp-containing egg white produced by GM chickens. Total and Cj allergen (Cry j 1)-specific IgE levels were significantly decreased in allergic mice fed with cLys-7crp-containing egg white compared with allergic mice fed with normal egg white. These results suggest that oral administration of T-cell epitope-containing egg white derived from GM chickens is effective for the induction of immune tolerance as an allergy therapy.
Highlights
Japanese cedar (Cryptomeria japonica; Cj) pollinosis is a serious type I allergic disease in Japan [1]
This study aims to investigate whether oral tolerance against Cj pollinosis can be induced using egg white containing T-cell epitopes produced by genetically manipulated (GM) chickens
We constructed a retroviral vector plasmid, pQMSCV/ DALys-7crp/internal ribosomal entry site (IRES)/enhanced green fluorescence protein (EGFP), encoding a bicistronic expression cassette of chicken egg white lysozyme (cLys)-7crp and EGFP mediated by IRES under the control of chicken b-actin promoter
Summary
Japanese cedar (Cryptomeria japonica; Cj) pollinosis is a serious type I allergic disease in Japan [1]. Type I allergic diseases, including Cj pollinosis, are characterized by the elevation of immunoglobulin E (IgE) levels and mast cell degranulation, followed by the release of histamine and other chemical mediators of allergy [3]. A stepwise subcutaneous administration of an escalating dose of the specific crude allergen extracts has been used for the treatment for allergies. This therapy has some disadvantages, such as the requirement of long-term administration of allergens under the control of physicians and the possibility of triggering an adverse reaction such as acute anaphylaxis by allergen administration [5,6]. It is highly desirable to establish a more convenient and curative immunotherapy
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have