Reconstitution of a novel recombinant Marek's disease virus as a vector vaccine against poultry red mites

• Project/Area Number: 16K18798
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: Shiro Murata 北海道大学, 獣医学研究科, 助教 (10579163)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ワクモ / 組換えワクチン / マレック病 / マレック病ウイルス / 感染性クローン / 組換えウイルス / 弱毒生ワクチン / 外部寄生虫

Outline of Final Research Achievements

The poultry red mite (PRM), is one of the major hematophagous ectoparasites of poultry farming, and the decreased productivity due to blood-sucking by PRMs is a severe problem for the poultry industry. The use of acaricides often leads to the spread of acaricide-resistant PRMs. Therefore, alternative strategies are required to reduce economic losses in poultry farming. Here, we focus on preventive methods such as vaccination to control PRMs, and we have already identified several vaccine candidates. In order to prepare an easy-to-use anti-PRM vaccine, the recombinant Marek's disease (MD) virus (rMDV) expressing a vaccine antigen was reconstituted. Reconstituted rMDV showed no significant differences in the growth kinetics compared to the parental strain, and the vaccine antigen was expressed in the infected cells. Thus, the rMDV live vaccine expressing a vaccine antigen against PRMs may be applicable as a candidate dual vaccine that provides protection against both PRMs and MD.

Research Products

• [Journal Article] Molecular detection and phylogenetic analysis of Ehrlichia canis in Philippine dogs (2018)
  • Author(s): Maekawa N, Konnai S, Balbin MM, Mingala CN, Gicana KRB, Bernando FAEM, Murata S, Ohashi K
  • Journal Title: Ticks Tick Borne Dis Volume: 9(2) Issue: 2 Pages: 266-269
  • DOI: 10.1016/j.ttbdis.2017.09.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prostaglandin E2 induction suppresses the Th1 immune responses in cattle with Johne's disease. (2018)
  • Author(s): Sajiki Y, Konnai S, Okagawa T, Nishimori A, Maekawa N, Goto S, Ikebuchi R, Nagata R, Kawaji S, Kagawa Y, Yamada S, Kato Y, Nakajima C, Suzuki Y, Murata S, Mori Y, Ohashi K.
  • Journal Title: Infect. Immun. Volume: in press Issue: 5
  • DOI: 10.1128/iai.00910-17
  • Peer Reviewed
• [Journal Article] Identification of immuno-inhibitory molecules in Mongolian native cattle and yak (2018)
  • Author(s): Ochirkhuu N, Konnai S, Odbileg R, Okagawa T, Maekawa N, Murata S, Ohashi K.
  • Journal Title: Jap. J. Vet. Res. Volume: in press
  • NAID: 120006498199
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1) rat-bovine chimeric antibody against bovine leukemia virus infection. (2017)
  • Author(s): Nishimori A, Konnai S, Okagawa T, Maekawa N, Ikebuchi R, Goto S, Sajiki Y, Suzuki Y, Kohara J, Ogasawara S, Kato Y, Murata S, Ohashi K.
  • Journal Title: PLoS One Volume: 印刷中 Issue: 4 Pages: e0174916-e0174916
  • DOI: 10.1371/journal.pone.0174916
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increase of cells expressing PD-1 and PD-L1 and enhancement of IFN-γ production via PD-1/PD-L1 blockade in bovine mycoplasmosis (2017)
  • Author(s): Goto Shinya、Konnai Satoru、Okagawa Tomohiro、Nishimori Asami、Maekawa Naoya、Gondaira Satoshi、Higuchi Hidetoshi、Koiwa Masateru、Tajima Motoshi、Kohara Junko、Ogasawara Satoshi、Kato Yukinari、Suzuki Yasuhiko、Murata Shiro、Ohashi Kazuhiko
  • Journal Title: Immunity, Inflammation and Disease Volume: 5 Issue: 3 Pages: 355-363
  • DOI: 10.1002/iid3.173
  • NAID: 120006711664
  • Peer Reviewed / Open Access
• [Journal Article] Anti-Bovine Programmed Death-1 Rat-Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle. (2017)
  • Author(s): Okagawa, T., Konnai, S., Nishimori, A., Maekawa, N., Ikebuchi, R., Goto, S., Nakajima, C., Kohara, J., Ogasawara, S., Kato, Y., Suzuki, Y., Murata, S. and Ohashi, K.
  • Journal Title: Front Immunol. Volume: 8 Pages: 650-650
  • DOI: 10.3389/fimmu.2017.00650
  • NAID: 120006370596
  • Peer Reviewed / Open Access
• [Journal Article] Identification of an atypical enzootic bovine leukosis in Japan by using a novel classification of bovine leukemia based on immunophenotypic analysis. (2017)
  • Author(s): Nishimori, A., Konnai, S., Okagawa, T., Maekawa, N., Goto, S., Ikebuchi, R., Nakahara, A., Chiba, Y., Ikeda, M., Murata, S. and Ohashi, K.
  • Journal Title: Clin. Vaccine Immunol. Volume: CVI.00067-17. Issue: 9
  • DOI: 10.1128/cvi.00067-17
  • Peer Reviewed / Open Access
• [Journal Article] Molecular Epidemiological Survey and Genetic Characterization of Anaplasma Species in Mongolian Livestock (2017)
  • Author(s): Ochirkhuu Nyamsuren、Konnai Satoru、Odbileg Raadan、Murata Shiro、Ohashi Kazuhiko
  • Journal Title: Vector Borne Zoonotic Dis. Volume: 17 Issue: 8 Pages: 539-549
  • DOI: 10.1089/vbz.2017.2111
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma (2017)
  • Author(s): Maekawa Naoya、Konnai Satoru、Takagi Satoshi、Kagawa Yumiko、Okagawa Tomohiro、Nishimori Asami、Ikebuchi Ryoyo、Izumi Yusuke、Deguchi Tatsuya、Nakajima Chie、Kato Yukinari、Yamamoto Keiichi、Uemura Hidetoshi、Suzuki Yasuhiko、Murata Shiro、Ohashi Kazuhiko
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 8951-8951
  • DOI: 10.1038/s41598-017-09444-2
  • Peer Reviewed / Open Access
• [Journal Article] Molecular epidemiological survey and genetic characterization of <i>ovine</i> <i>gammaherpesvirus-2</i> in Mongolian livestock (2017)
  • Author(s): OCHIRKHUU Nyamsuren、KONNAI Satoru、ODBILEG Raadan、MURATA Shiro、OHASHI Kazuhiko
  • Journal Title: Journal of Veterinary Medical Science Volume: 79 Issue: 12 Pages: 2040-2042
  • DOI: 10.1292/jvms.17-0203
  • NAID: 130006267592
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intrauterine infection with bovine leukemia virus in pregnant dam with high viral load (2017)
  • Author(s): Sajiki Y, Konnai S, Nishimori A, Okagawa T, Maekawa N, Goto S, Nagano M, Kohara J, Kitano N, Takahashi T, Tajima M, Mekata H, Horii Y, Murata S, Ohashi K.
  • Journal Title: Journal of Veterinary Medical Science Volume: 79 Issue: 12 Pages: 2036-2039
  • DOI: 10.1292/jvms.17-0391
  • NAID: 130006267604
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Journal Article] Detection and molecular characterization of equine infectious anemia virus in Mongolian horses (2017)
  • Author(s): SHARAV Tumenjargal、KONNAI Satoru、OCHIRKHUU Nyamsuren、TS Erdene Ochir、MEKATA Hirohisa、SAKODA Yoshihiro、UMEMURA Takashi、MURATA Shiro、CHULTEMDORJ Tungalag、OHASHI Kazuhiko
  • Journal Title: Journal of Veterinary Medical Science Volume: 79 Issue: 11 Pages: 1884-1888
  • DOI: 10.1292/jvms.17-0202
  • NAID: 130006206580
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Isolation and purification of <i>Gallid herpesvirus</i> 2 strains currently distributed in Japan (2017)
  • Author(s): Machida Y, Murata S, Matsuyama-Kato A, Isezaki M, Taneno A, Sakai E, Konnai S, Ohashi K.
  • Journal Title: Journal of Veterinary Medical Science Volume: 79 Issue: 1 Pages: 115-122
  • DOI: 10.1292/jvms.16-0329
  • NAID: 130005289788
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Journal Article] Immune exhaustion during chronic infections in cattle (2017)
  • Author(s): Konnai S, Murata S, Ohashi K.
  • Journal Title: Journal of Veterinary Medical Science Volume: 79 Issue: 1 Pages: 1-5
  • DOI: 10.1292/jvms.16-0354
  • NAID: 130005289790
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cooperation of PD-1 and LAG-3 Contributes to T-Cell Exhaustion in Anaplasma marginale-Infected Cattle (2016)
  • Author(s): Okagawa T, Konnai S, Deringer JR, Ueti MW, Scoles GA, Murata S, Ohashi K, Brown WC.
  • Journal Title: Infect Immun. Volume: 84(10) Issue: 10 Pages: 2779-2790
  • DOI: 10.1128/iai.00278-16
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 日本に分布するマレック病ウイルスの分離と性状解析 (2017)
  • Author(s): 村田史郎、町田柚香、種子野章、酒井英史、松山あゆ美、伊勢崎政美、今内覚、大橋和彦
  • Organizer: 平成29年度 鶏病研究会北海道支部技術検討会
• [Presentation] 日本国内における牛白血病発症牛の分類と表現型解析 (2017)
  • Author(s): 西森朝美、今内 覚、岡川朋弘、前川直也、池渕良洋、後藤伸也、佐治木大和、村田史郎、大橋和彦
  • Organizer: 日本ウイルス学会北海道支部会第51回夏季シンポジウム
• [Presentation] 牛白血病ウイルス（BLV）感染症におけるプロスタグランジンE2（PGE2）の動態および機能解析 (2017)
  • Author(s): 佐治木大和、今内 覚、西森朝美、岡川朋弘、前川直也、池渕良洋、後藤伸也、村田史郎、大橋和彦
  • Organizer: 日本ウイルス学会北海道支部会第51回夏季シンポジウム
• [Presentation] Enhanced immune responses after vaccination with a gallid alphaherpesvirus 2 (Marek’s disease virus, MDV) expressing PD-1 (2017)
  • Author(s): Shiro Murata, Benedikt B Kaufer, Nikolaus Osterrieder, Masayoshi Isezaki, Satoru Konnai and Kazuhiko Ohashi
  • Organizer: 42nd International Herpesvirus Workshop
  • Int'l Joint Research
• [Presentation] 牛白血病ウイルス（BLV）感染ハイリスク牛における初めての子宮内感染直接証明 (2017)
  • Author(s): 佐治木大和、 今内 覚、 西森朝美、 岡川朋弘、 永野昌志、 小原潤子、 村田史郎、大橋和彦
  • Organizer: 平成29年度北海道地区ならびに第68回北海道獣医師大会
• [Presentation] BLV感染症をモデルとした抗ウシPD-L1キメラ抗体の臨床応用試験 (2017)
  • Author(s): 西森朝美、今内覚、岡川朋弘、前川直也、池渕良洋、後藤伸也、佐治木大和、鈴木定彦、小原潤子、小笠原諭、加藤幸成、村田史郎、大橋和彦
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] 牛白血病ウイルス（BLV)感染症においてプロスタグランジンE2（PGE2）が及ぼす免疫抑制機序の解明 (2017)
  • Author(s): 佐治木大和、今内覚、西森朝美、岡川朋弘、村田史郎、大橋和彦
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] COX-2阻害薬と抗PD-L1抗体の併用によるイヌ腫瘍疾患の制御法の検討 (2017)
  • Author(s): 浅野裕美恵、今内覚、岡川朋弘、前川直也、西森朝美、後藤伸也、高木哲、村田史郎、大橋和彦
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] マレック病ウイルス弱毒株を用いた新規抗ワクモワクチン開発に向けた基礎研究 (2017)
  • Author(s): 青山珠里愛、村田史郎、伊勢崎政美、種子野章、酒井英史、今内覚、大橋和彦
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] PD-L1を標的としたイヌ用キメラ抗体医薬の作製と悪性黒色腫および未分化肉腫罹患犬における抗腫瘍効果の検討 (2017)
  • Author(s): 前川直也、今内覚、高木哲、賀川由美子、岡川朋弘、西森朝美、池渕良洋、和泉雄介、出口辰弥、加藤幸成、鈴木定彦、村田史郎、大橋和彦
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] 日本に分布するマレック病ウイルス野外株の病原性の検討 (2017)
  • Author(s): 村田史郎、種子野章、酒井英史、町田柚香、松山あゆ美、伊勢崎政美、今内覚、大橋和彦
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] 牛マイコプラズマ感染症における免疫抑制機序の解明 (2017)
  • Author(s): 後藤 伸也, 今内 覚, 岡川 朋弘, 西森 朝美, 前川 直也, 樋口 豪紀, 小岩 政照, 田島 誉士, 小原 潤子, 加藤 幸成, 鈴木 定彦, 村田 史郎, 大橋 和彦
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] Theileria parva感染症における免疫チェックポイント因子の動態解析 (2017)
  • Author(s): 今内 覚、岡川朋弘、山田慎二、Martin Simuunza, Timothy Connelley, Ivan Morrison, 村田史郎、大橋和彦
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] 牛のアナプラズマ病における免疫疲弊機序の解明 (2017)
  • Author(s): 岡川朋弘、今内覚、James R. Deringer、Massaro W. Ueti、Glen A. Scoles、村田史郎、大橋和彦、Wendy C. Brown
  • Organizer: 第63回寄生虫/衛生動物学会 北日本支部合同大会
• [Presentation] ワクモ（Dermanysus gallinae）由来 カテプシンL様タンパク質の性状解析とワクチン抗原としての評価 (2017)
  • Author(s): 村田史郎、伊勢崎政美、谷口綾香、北條巧、種子野章、酒井英史、宇野有紀子、市居修、伊東拓也、今内 覚、大橋 和彦
  • Organizer: 第63回寄生虫/衛生動物学会 北日本支部合同大会
• [Presentation] マレック病ウイルス日本分離株の全ゲノム解析 (2016)
  • Author(s): 村田史郎、町田柚香、伊勢崎政美、今内覚、大橋和彦
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学、藤沢市
  • Year and Date: 2016-09-06
• [Presentation] 抗ワクモ（Dermanyssus gallinae）ワクチン開発に向けたワクモ由来フェリチン２の性状解析 (2016)
  • Author(s): 伊勢崎政美、村田史郎、酒井英史、矢吹卓也、種子野章、市居修、伊東拓也、今内覚、大橋和彦
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学、藤沢市
  • Year and Date: 2016-09-06
• [Presentation] シュルツェマダニ（Ixodes Persulcatus) 由来sialostatinL2の機能解析 (2016)
  • Author(s): 越智晶絵、今内覚、伊東拓也、川端寛樹、高野愛、安藤秀二、村田史郎、大橋和彦
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学、藤沢市
  • Year and Date: 2016-09-06
• [Presentation] ウシ腫瘍壊死因子（TNF-a）デコイレセプターによる新規抗炎症剤の開発 (2016)
  • Author(s): 藤澤宗太郎、今内覚、岡川朋弘、西森朝美、前川直也、村田史郎、鈴木定彦、大橋和彦
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学、藤沢市
  • Year and Date: 2016-09-06
• [Presentation] 家畜における免疫チェックポイント関連因子の遺伝子比較解析とウシ用抗体を用いた動物種横断的研究 (2016)
  • Author(s): 野島裕太郎、今内覚、岡川朋弘、西森朝美、前川直也、森康行、賀川由美子、鈴木定彦、村田史郎、大橋和彦
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学、藤沢市
  • Year and Date: 2016-09-06
• [Presentation] ウシCytotoxic T-lymphocyte antigen-4 (CTLA-4) の機能解析と特異抗体の樹立 (2016)
  • Author(s): 渡慧、今内覚、前川直也、岡川朋弘、西森朝美、鈴木定彦、村田史郎、大橋和彦
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学、藤沢市
  • Year and Date: 2016-09-06
• [Presentation] Molecular detection and characterization of bovine viral diarrhea virus in Mongolian cattle and yaks (2016)
  • Author(s): Ochirkhuu Nyamsuren, 今内覚、Odbileg Raadan, 村田史郎, 大橋和彦
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学、藤沢市
  • Year and Date: 2016-09-06
• [Presentation] Sequence analysis of a Marek's disease virus strain isolated in Japan (2016)
  • Author(s): Shiro Murata, Yuka Machida, Masayoshi Isezaki, Satoru Konnai, Kazuhiko Ohashi
  • Organizer: 11th International Symposium on Marek's Disease and Avian Herpesviruses
  • Place of Presentation: Tours, France
  • Year and Date: 2016-07-06
  • Int'l Joint Research
• [Presentation] The Role of Meq Mutations on Marek's Disease Virus Pathogenesis (2016)
  • Author(s): Nirajan Bhandari, Phaedra Tavlarides-Hontz, Upendra Katneni, Benedikt B. Kaufer, Shiro Murata, Mark S. Parcells
  • Organizer: 11th International Symposium on Marek's Disease and Avian Herpesviruses
  • Place of Presentation: Tours, France
  • Year and Date: 2016-07-06
  • Int'l Joint Research