Effect of Cry-consensus peptide, a novel recombinant peptide for immunotherapy of Japanese cedar pollinosis, on an experimental allergic rhinitis model in B10.S mice.
BACKGROUND
We are developing an immunotherapeutic peptide, Cry-consensus peptide, for Japanese cedar pollinosis. Cry-consensus peptide is a recombinant polypeptide containing six major human T-cell epitopes derived from both Cry j 1 and Cry j 2, two major allergens of Japanese cedar pollen. We examined the effect of Cry-consensus peptide on an allergic rhinitis model in B10.S mice, which have one common T-cell epitope in the Cry-consensus peptide.


METHODS
B10.S mice were sensitized with Cry j 1/alum, then the Cry-consensus peptide was administered subcutaneously once a week for 5 weeks from the last sensitization. Histamine was dropped in both nostrils (10 microL per nostril) of each mouse on the day before continuous intranasal instillation of Cry j 1. Soon after the final challenge with Cry j 1, the mice were observed for 5 minutes for the resulting number of sneezes. In addition, serum levels of Cry j 1-specific IgE and IgG2a antibody, eosinophil infiltration in nasal tissue, and Cry j 1-specific cytokine production from splenocytes were evaluated.


RESULTS
Cry-consensus peptide markedly inhibited Cry j 1-induced sneezes, eosinophil infiltration, and eosinophil peroxidase (EPO) activity in nasal tissue. Cry-consensus peptide inhibited the production of anti-Cry j 1 IgE (Th2-mediated) and significantly enhanced anti-Cry j 1 IgG2a (Th1-mediated). In cytokine production from splenocytes, Cry-consensus peptide significantly decreased in IL-4/IFN-gamma and IL-5/IFN-gamma ratios.


CONCLUSIONS
It was concluded that Cry-consensus peptide effectively controlled allergic responses, which results from shifting from a Th2-dominated to a Th1-dominated immune response.
Tsunematsu
Masako
M
Research and Development Center, Division of Research and Development, Meiji Dailies Corporation, Odawara, Kanagawa, Japan. MASAKO_TSUNEMATSU@MEIJI-MILK.COM
Yamaji
Taketo
T
Kozutsumi
Daisuke
D
Murakami
Rika
R
Kimura
Shigeki
S
Kino
Kohsuke
K
D000485:Allergens / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000818:Animals; D032485:Cryptomeria / Q000276:immunology*; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007564:Japan; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011058:Pollen / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D059470:Tetraspanins
D000485:Allergens; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D011994:Recombinant Proteins; D059470:Tetraspanins; C528335:Tspan13 protein, mouse; C518796:cry-consensus peptide