Study on vaccine using food allergen-producing lactic acid bacterium in food allergy

• Project/Area Number: 15K07756
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Azabu University
• Principal Investigator: Sakaguchi Masahiro 麻布大学, 獣医学部, 教授 (20170590)
• Co-Investigator(Kenkyū-buntansha): 五十君 静信 国立医薬品食品衛生研究所, 食品衛生管理部, 客員研究員 (70212743)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 食物アレルギー / オボアルブミン / 乳酸菌 / イヌ / マウス / 卵 / アレルゲン

Outline of Final Research Achievements

Ovalbumin (OVA)-producing lactic acid bacteria (LB) were orally administrated to mice, followed by an intraperitoneal injection of OVA and alum. There were no differences in the levels of OVA-specific IgE between the group that received OVA-producing LB and the control groups, suggesting that the OVA-producing ability of these LB was low. Next, a mixture of OVA and LB was administered orally to mice. We found that the administration of more than 10 μg of OVA suppresses the levels of OVA-specific IgE. Mixtures of OVA and LB may therefore be used in immunotherapy for egg allergies. We then measured the levels of IgE specific to egg allergens in 82 dogs with food allergies. Approximately 10% of these dogs produced IgE specific to crude white egg. Furthermore, 75% of dogs with IgE specific to crude white egg also produced OVA-specific IgE. This suggests that a mixture of egg allergens and LB could be used in immunotherapy for food allergy in dogs.

Research Products

• [Int'l Joint Research] ウィスコンシン 大学(アメリカ)
• [Journal Article] Time dependent distinct roles of Toll-like receptor 4 in a house-dust-mite-induced asthma mouse model (2018)
  • Author(s): Ishii T.、Niikura Y.、Kurata K.、Muroi M.、Tanamoto K.、Nagase T.、Sakaguchi M.、Yamashita N.
  • Journal Title: Scandinavian Journal of Immunology Volume: 87 Pages: 1-7
  • DOI: 10.1111/sji.12641
  • Peer Reviewed / Open Access
• [Journal Article] Piperacillin and ceftazidime produce the strongest synergistic phage antibiotic effect in Pseudomonas aeruginosa (2018)
  • Author(s): Uchiyama J, Shigehisa R, Nasukawa T, Mizukami K, Takemura-Uchiyama I, Ujihara T, Murakami H, Imanishi I, Nishifuji K, Sakaguchi M, Matsuzaki S.
  • Journal Title: Archives of Virology Volume: in press Pages: 1941-1948
  • DOI: 10.1007/s00705-018-3811-0
  • Peer Reviewed / Open Access
• [Journal Article] Identification of the PLA2G6 c.1579G>A missense mutation in papillon dog neuroaxonal dystrophy using whole exome sequencing analysis. (2017)
  • Author(s): Tsuboi M, Watanabe M, Nibe K, Yoshimi N, Kato A, Sakaguchi M, Yamato O, Tanaka M, Kuwamura M, Kushida K, Ishikura T, Harada T, Chambers JK, Sugano S, Uchida K, Nakayama H.
  • Journal Title: Plos one Volume: 12 Pages: 1-17
  • DOI: 10.1371/journal.pone.0169002
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Bovine leukemia virus G4 enhances virus production. (2017)
  • Author(s): Murakami H, Asano S, Uchiyama J, Sato R, Sakaguchi M, Tsukamoto K.
  • Journal Title: Virus Research Volume: 238 Pages: 213-217
  • DOI: 10.1016/j.virusres.2017.07.005
  • Peer Reviewed / Open Access
• [Journal Article] Adsorption of Staphylococcus viruses S13' and S24-1 on Staphylococcus aureus strains with different glycosidic linkage patterns of wall teichoic acids (2017)
  • Author(s): Uchiyama, J., Taniguchi, M., Kurokawa, K., Takemura-Uchiyama, I., Ujihara, T., Shimakura, H., Sakaguchi, Y., Murakami, H., Sakaguchi, M., Matsuzaki, S.
  • Journal Title: Journal of General Virology Volume: 98(8) Pages: 2171-2180
  • DOI: 10.1099/jgv.0.000865
  • Peer Reviewed / Open Access
• [Journal Article] Analyses of short-term antagonistic evolution of Pseudomonas aeruginosa strain PAO1 and phage KPP22 (Myoviridae family, PB1-like virus genus). (2016)
  • Author(s): Ryu Shigehisa, Jumpei Uchiyama, Shin-ichiro Kato, Iyo Takemura-Uchiyama, Kotoe Yamaguchi, Reina Miyata, Takako Ujihara, Yoshihiko Sakaguchi, Noriaki Okamoto, Hidekatsu Shimakura, Masanori Daibata, Masahiro Sakaguchi, Shigenobu Matsuzaki.
  • Journal Title: App. Environ. Microbiol. Volume: 60 Pages: 4482-4491
  • DOI: 10.1111/1348-0421.12347
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cross-reactivity between major IgE core epitopes on Cry j 2 allergen of Japanese cedar pollen and relevant sequences on Cha o 2 allergen of Japanese cypress pollen (2016)
  • Author(s): Miyaji, K., Okamoto, N., Saito, S., Yasueda, H., Takase, Y., Shimakura, H., Saito, S., and Sakaguchi, M.
  • Journal Title: Allergol. Int. Volume: ６５ Issue: 3 Pages: 286-292
  • DOI: 10.1016/j.alit.2016.01.003
  • NAID: 130005165887
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Analyses of short-term antagonistic evolution between Pseudomonas aeruginosa strain PAO1 and phage KPP22 belonging to family Myoviridae genus PB1-like viruses. (2016)
  • Author(s): Uchiyama J, Suzuki M, Nishifuji K, Kato S, Miyata R, Nasukawa T, Yamaguchi K, Takemura-Uchiyama I, Ujihara T, Shimakura H, Murakami H, Okamoto N, Sakaguchi Y, Shibayama K, Sakaguchi M, Matsuzaki S.
  • Journal Title: Applied and Environmental Microbiology Volume: 82 Pages: 4482-4491
  • DOI: 10.1128/aem.00090-16
  • Peer Reviewed / Open Access
• [Journal Article] Screening of KHP30-like prophage among Japanese Helicobacter pylori strains, and genetic analysis of a defective KHP30-like prophage sequence integrated in the genome of the Helicobacter pylori strain NY40. (2016)
  • Author(s): Uchiyama J, Takemura-Uchiyama I, Kato S, Takeuchi H, Sakaguchi Y, Ujihara T, Daibata M, Shimakura H, Okamoto N, Sakaguchi M, Matsuzaki S.
  • Journal Title: FEMS Microbiol. Lett. Volume: 363 Pages: 1-9
  • DOI: 10.1093/femsle/fnw157
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IgE reactivity to hen’s egg white allergens in dogs with cutaneous adverse food reactions. (2016)
  • Author(s): Shimakura, H., Saito, T., Uchiyama, J., Miyaji, K., Fujimura, M., Masuda, K., Okamoto, N., DeBoer, D.J., Sakaguchi, M.
  • Journal Title: Veterinary Immunology and Immunopathology Volume: 177 Pages: 52-57
  • DOI: 10.1016/j.vetimm.2016.06.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inefficient viral replication of bovine leukemia virus induced by spontaneous deletion mutation on G4 gene. (2016)
  • Author(s): Murakami, H., Uchiyama, J., Nikaido, S., Sato, R., Sakaguchi, M., Tsukamoto, K.
  • Journal Title: Journal of General Virology Volume: 97 Pages: 2753-2762
  • DOI: 10.1099/jgv.0.000583
  • Peer Reviewed / Open Access
• [Journal Article] Nationwide distribution of bovine influenza D virus infection in Japan. (2016)
  • Author(s): Horimoto T, Hiono T, Mekata H, Odagiri T, Lei Z, Kobayashi T, Norimine J, Inoshima Y, Hikono H, Murakami K, Sato R, Murakami H, Sakaguchi M, Ishii K, Ando T, Otomaru K, Ozawa M, Sakoda Y, Murakami S.
  • Journal Title: Plos one Volume: 11 (9) Pages: 1-7
  • DOI: 10.1371/journal.pone.0163828
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cross-reactivity between major IgE core epitopes on Cry j 2 allergen of Japanese cedar pollen and relevant sequences on Cha o 2 allergen of Japanese cypress pollen (2016)
  • Author(s): Miyaji, K., Okamoto, N., Saito, S., Yasueda, H., Takase, Y., Shimakura, H., Saito, S., and Sakaguchi, M.
  • Journal Title: Allergology International Volume: in press
  • NAID: 130005165887
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Analysis of KHP30-like prophage in the genome of Helicobacter 4 pylori strain NY40. (2016)
  • Author(s): Uchiyama, J , Takemura-Uchiyama, I., Kato, S., Takeuchi, H., Sakaguchi, Y., Ujihara, T., Daibata, M., Shimakura, H., Okamoto, N., Sakaguchi, M., Matsuzaki, S.
  • Journal Title: FEMS Microbiology Letters Volume: in press
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Japanese Society of Allergology task force report on standardization of house dust mite allergen vaccines - Secondary publication (2015)
  • Author(s): Takai T, Okamoto Y, Okubo K, Nagata M, Sakaguchi M, Fukutomi Y, Saito A, Yasueda H, Masuyama K
  • Journal Title: Allergol. Int. Volume: 64(2) Issue: 2 Pages: 181-186
  • DOI: 10.1016/j.alit.2015.01.005
  • NAID: 130005290283
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Cats as a potential source of emerging influenza virus infections. (2015)
  • Author(s): Horimoto. T., Gen, F., Murakami, S., Iwatsuki-Horimoto, K., Kato, K., Hisasue, M., Sakaguchi, M., Nidom, C.A., and Kawaoka, Y
  • Journal Title: Virol Sin Volume: ３０ Pages: 221-223
  • DOI: 10.1007/s12250-015-3580-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 遺伝的変化がもたらす牛白血病ウイルスの伝播力への影響 (2018)
  • Author(s): 村上裕信、内山淳平、鈴木千裕、二階堂紗恵、渋谷夏帆、佐藤礼一郎、前田洋佑、富岡美千子、竹嶋伸之輔、加藤肇、阪口雅弘、泉對博、間陽子、塚本健司
  • Organizer: H29年度日本獣医師会学術集会
• [Presentation] イヌにおけるワクチン接種後のアレルギー副反応に関する疫学調査 (2018)
  • Author(s): 伊藤 雅人,水上 圭二郎,内山 淳平, 阪口 雅弘
  • Organizer: 第14回日本獣医内科アカデミー
• [Presentation] 花粉飛散時期における室内飼育犬の被毛への花粉付着と除去の検討 (2018)
  • Author(s): 白井 秀治, 中村 恒彰, 磯田 由美, 相場 美咲, 黒崎 勉, 阪口 雅弘
  • Organizer: 第14回日本獣医内科アカデミー
• [Presentation] Study of adsorption of AHJD-like phages infecting Staphylococcus aureus (2017)
  • Author(s): Jumpei Uchiyama, Kenshi Kurokawa, Iyo Takemura-Uchiyama, Takako Ujihara, Yoshihiko Sakaguchi, Masahiro Sakaguchi, Shigenobu Matsuzaki
  • Organizer: 第９０回日本細菌学会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-19
• [Presentation] 犬アトピー性皮膚炎症例におけるEnterococcus faecalis FK-23投与と臨床症状の変化にする研究 多施設実施二重盲検無作為プラセボ比較試験 (2017)
  • Author(s): 大隅尊史、阪口雅弘、嶋田貴志、辻本元
  • Organizer: 第20回獣医皮膚科学学会
  • Place of Presentation: 大宮
  • Year and Date: 2017-03-11
• [Presentation] 実験動物アレルギーにおける診断と治療 (2017)
  • Author(s): 阪口雅弘
  • Organizer: 第94回実験動物コンファレンス
  • Invited
• [Presentation] 普遍形質導入による黄色ブドウ球菌の進化可能性検討 (2017)
  • Author(s): 内山淳平、内山伊代、中森洋佑、水上圭二郎、阪口雅弘、松崎茂展
  • Organizer: MRSAフォーラム2017
• [Presentation] Analysis of adsorption of phages, S13and and S24-1, belonging to the family Podoviridae genus P68virus, using Staphylococcus aureus strains with different glycosidic linkage patterns of wall teichoic acids (2017)
  • Author(s): Uchiyama J, Kurokawa K, Takemura-Uchiyama I, Ujihara T, Sakaguchi Y, Sakaguchi M, Matsuzaki S
  • Organizer: International Union of Microbiological Societies 2017
  • Int'l Joint Research
• [Presentation] Virus purification by CsCl density gradient using general centrifugation (2017)
  • Author(s): Nasukawa T, Uciyama J, Taharaguchi S, Ota S, Ujihara T, Matsuzaki S, Murakami H, Mizukami K, Sakaguchi M
  • Organizer: 16th Awaji International Forum on Infection and Immunity
  • Int'l Joint Research
• [Presentation] ワンヘルスにおけるヒトと動物のアレルギー疾患 (2017)
  • Author(s): 阪口雅弘
  • Organizer: 第1回日本ワンヘルスサイエンス学会
  • Invited
• [Presentation] 花粉飛散時期における室内飼育犬の被毛への花粉付着の検討 (2017)
  • Author(s): 白井秀治、中村恒彰、磯田由美、相場美咲、阪口雅弘
  • Organizer: 第160回日本獣医学会
• [Presentation] 日本における伴侶動物の遺伝子関連疾患研究のための犬の遺伝子（DNA)バンクについて (2017)
  • Author(s): 阪口雅弘
  • Organizer: 第160回日本獣医学会
  • Invited
• [Presentation] 犬のアトピー性皮膚炎の遺伝的解析 (2017)
  • Author(s): 村上裕信、佐々木慎二、阪口雅弘
  • Organizer: 第160回日本獣医学会
• [Presentation] H7亜型鳥インフルエンザを迅速かつ網羅的に検出するLAMP法の開発 (2017)
  • Author(s): 野口きらら 、高橋ゆきの 、古山雄平 、久松伸 、阪口雅弘 、村上裕信 、塚本健司
  • Organizer: 第160回日本獣医学会
• [Presentation] The Mutant Allele frequency of the canine TUBB1:c.5G>A Associated with Asymptomatic Macrothrombocytopenia in Norfolk and Cairn Terriers in Japan (2017)
  • Author(s): Kinjo S, Takahashi M, Yamato O, Sakaguchi M, Mizukami K, Tsujimoto H, Endo Y
  • Organizer: Asia Meeting of Animal Medicine Specialities 2017
  • Int'l Joint Research
• [Presentation] DogFilerを用いた犬種推定法の検討 (2016)
  • Author(s): 旭 愛、岡本憲明、関口和正、阪口雅弘、武内ゆかり、松田秀明
  • Organizer: 第22回日本法科学技術学会
  • Place of Presentation: 東京
  • Year and Date: 2016-11-10
• [Presentation] Serological survey reveals the wide distribution of bovine influenza D virus infection in Japan (2016)
  • Author(s): Taisuke Horimoto, Tomoha Odagiri, Zhihao Lei, Tomoya Kobayashi, Maiko Endo, Akiko Uema, Hirohisa Mekata, Junzo Norimine, Kenji Murakami, Hironobu Murakami, Masahiro Sakaguchi, Kazunori Ishii, Yasuo Inoshima, Makoto Ozawa, Takahiro Hiono, Yoshihiro Sakoda, Benjamin Hause, Shin Murakami
  • Organizer: 第64回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Presentation] ダニアレルゲンワクチン標準化に関する日本アレルギー学会タスクフォース報告 (2016)
  • Author(s): 高井敏朗、岡本美孝、大久保)公裕、永田真、阪口雅弘、福冨友馬、齋藤明美、安枝、浩、増山敬祐
  • Organizer: 第６５回日本アレルギー学会
  • Place of Presentation: 東京
  • Year and Date: 2016-06-17
• [Presentation] 食物有害反応を示す犬における卵白抗原に対するIgE反応性の検討 (2015)
  • Author(s): 島倉秀勝、齋藤拓、藤村正人 、岡本憲明、内山淳平、阪口雅弘
  • Organizer: 第158回日本獣医学会
  • Place of Presentation: 十和田
  • Year and Date: 2015-09-07
• [Book] 有害微生物の制御と管理 (2016)
  • Author(s): 阪口雅弘
  • Total Pages: 664
  • Publisher: テクノシステム