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Recombinant Fusion Allergens, Cry j 1 and Cry j 2 from Japanese Cedar Pollen, Conjugated with Polyethylene Glycol Potentiate the Attenuation of Cry j 1-Specific IgE Production in Cry j 1-Sensitized Mice and Japanese Cedar Pollen Allergen-Sensitized Monkeys. 2015

Takashi Fujimura, and Koji Fujinami, and Ryosuke Ishikawa, and Minoru Tateno, and Yoshio Tahara, and Yasushi Okumura, and Hisashi Ohta, and Hiroyuki Miyazaki, and Masaru Taniguchi
RIKEN-TORII Joint Research Team, RIKEN Center for Integrative Medical Sciences (IMS), RIKEN (The Institute of Physical and Chemical Research), Yokohama, Japan.

BACKGROUND Japanese cedar (Cryptomeria japonica) pollinosis is the most prevalent seasonal rhinitis in Japan. A standardized Japanese cedar pollen extract (CPE) containing 1.5-4.2 μg of Cry j 1 is currently the highest-concentration extract available for allergen-specific immunotherapy (SIT) against this pollinosis. Therefore, we developed a PEGylated fusion protein as a more effective SIT vaccine against Japanese cedar pollinosis. METHODS The fusion protein of major allergens for Japanese cedar pollen, Cry j 1 and Cry j 2, was expressed in Escherichia coli and conjugated with polyethylene glycol (PEG). The purified PEGylated Cry j 1/2 fusion protein (PEG-fusion) was subcutaneously injected four times into Cry j 1- sensitized mice and CPE-sensitized monkeys. The mice were then subcutaneously challenged with Cry j 1 and serum levels of Cry j 1-specific immunoglobulin, and the proliferation and cytokine production of splenocytes were analyzed. The monkeys were intranasally challenged with CPE and analyzed for Cry j 1-specific immunoglobulin levels in plasma. RESULTS Cry j 1-specific IgE was significantly attenuated in the PEG-fusion-treated group after Cry j 1-challenge and Cry j 1-specific IgG was significantly increased following PEG-fusion treatment in mice and monkeys. Proliferation and Th2-type cytokine production in splenocytes stimulated with Cry j 1 were also reduced in PEG-fusion-treated mice. IL10 and IL2 production were reduced, but not significantly, while IFN-x03B3; was significantly increased in the PEG-fusion-treated group. CONCLUSIONS A high-dose injection of PEG-fusion appears to be a valid candidate for a safer and more effective vaccine than the conventional SIT extract for Japanese cedar pollinosis.

UI MeSH Term Description Entries
D007073 Immunoglobulin E An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE). IgE
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010940 Plant Proteins Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which PLANT PROTEINS, DIETARY is available. Plant Protein,Protein, Plant,Proteins, Plant
D011058 Pollen The fertilizing element of plants that contains the male GAMETOPHYTES. Male Gametes, Plant,Male Gametophytes,Microspores, Plant,Plant Microspores,Pollen Grains,Gamete, Plant Male,Gametes, Plant Male,Gametophyte, Male,Gametophytes, Male,Grain, Pollen,Grains, Pollen,Male Gamete, Plant,Male Gametophyte,Microspore, Plant,Plant Male Gamete,Plant Male Gametes,Plant Microspore,Pollen Grain
D011092 Polyethylene Glycols Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS. Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D003888 Desensitization, Immunologic Immunosuppression by the administration of increasing doses of antigen. Though the exact mechanism is not clear, the therapy results in an increase in serum levels of allergen-specific IMMUNOGLOBULIN G, suppression of specific IgE, and an increase in suppressor T-cell activity. Allergen Immunotherapy,Allergy Shots,Hyposensitization Therapy,Immunotherapy, Allergen,Venom Immunotherapy,Immunologic Desensitization,Therapy, Hyposensitization,Allergen Immunotherapies,Allergy Shot,Desensitizations, Immunologic,Hyposensitization Therapies,Immunologic Desensitizations,Immunotherapy, Venom,Shot, Allergy,Venom Immunotherapies

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