Oral immunotherapy for pollen allergy using T-cell epitope-containing egg white derived from genetically manipulated chickens

Yoshinori Kawabe; Yuuki Hayashida; Kensaku Numata; Shota Harada; Yoshifumi Hayashida; Akira Ito; Masamichi Kamihira

doi:10.1371/journal.pone.0048512

Oral immunotherapy for pollen allergy using T-cell epitope-containing egg white derived from genetically manipulated chickens

PLoS One. 2012;7(10):e48512. doi: 10.1371/journal.pone.0048512. Epub 2012 Oct 29.

Authors

Yoshinori Kawabe¹, Yuuki Hayashida, Kensaku Numata, Shota Harada, Yoshifumi Hayashida, Akira Ito, Masamichi Kamihira

Affiliation

¹ Department of Chemical Engineering, Faculty of Engineering, Kyushu University, Fukuoka, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Allergens / genetics
Allergens / immunology*
Allergens / metabolism
Animals
Animals, Genetically Modified
Base Sequence
Blotting, Western
Chick Embryo
Chickens
Cryptomeria / immunology
Egg White*
Enzyme-Linked Immunosorbent Assay
Epitopes, T-Lymphocyte / genetics
Epitopes, T-Lymphocyte / immunology*
Epitopes, T-Lymphocyte / metabolism
Humans
Immunoglobulin E / blood
Immunoglobulin E / immunology
Immunotherapy / methods*
Mice
Molecular Sequence Data
Muramidase / genetics
Muramidase / immunology
Muramidase / metabolism
NIH 3T3 Cells
Pollen / immunology
Recombinant Fusion Proteins / administration & dosage
Recombinant Fusion Proteins / immunology*
Recombinant Fusion Proteins / metabolism
Rhinitis, Allergic, Seasonal / immunology*
Rhinitis, Allergic, Seasonal / therapy
Treatment Outcome

Substances

Allergens
Epitopes, T-Lymphocyte
Recombinant Fusion Proteins
Immunoglobulin E
Muramidase

Grants and funding

This work was supported in part by Grants-in-Aid for Scientific Research (nos. 18656245, 20360376, 23360372 and 23760753) from the Japan Society for the Promotion of Science and the Kieikai Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.