Development of subunit cocktail vaccine against bovine babesiosis

2018 Fiscal Year Annual Research Report

• Project/Area Number: 16H05033
• Research Institution: Obihiro University of Agriculture and Veterinary Medicine
• Principal Investigator: 横山 直明 帯広畜産大学, 原虫病研究センター, 教授 (80301802)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ウシバベシア / 牛 / 免疫原性 / 多型 / マダニ / オーダーメイド型

Outline of Annual Research Achievements

ウシバベシア原虫は牛の赤血球内に寄生し、増殖、破壊、再侵入を繰り返しながら、宿主に深刻な発熱、貧血、血色素尿、黄疸などの病害を引き起こす。しかし、いまだ有効なワクチンが開発されていない。本研究課題では、申請者がこれまで見いだしてきた研究シーズ（赤血球侵入に関わるワクチン候補原虫分子群、侵入分子群の遺伝子多型性、オーダーメイド型ワクチン戦略、新たな赤血球侵入評価系）を活用して、バベシアによる赤血球侵入を２段階で阻止できるサブユニットカクテルワクチンの開発を目指す。特に、野外で蔓延するバベシアの様々な遺伝子型を簡便に検出できるタイピングPCR法も完成させて、汚染国に適したオーダーメイド型の牛バベシア病ワクチンの開発プロトコールを確立し、そのワクチン戦略を世界に提示する。

最終年度では、1)新たに発見された病原性ウシバベシア種の世界分布と感染宿主を解明し、２）ウシバベシアのワクチン候補抗原の牛における免疫原性を確認し、３）世界に分布するウシバベシアのワクチン候補抗原の多型を整理し、４）ウシバベシアのマダニ感染系を確立し、さらには５）遺伝子組換えウシバベシア原虫の作出にも成功した。これらの研究結果はサブユニットカクテルワクチンの開発に向けて極めて有効な基盤成果となった。しかしながら、汚染国に適したオーダーメイド型の牛バベシア病ワクチンの開発プロトコールを完成するまでは至らなかった。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] モンゴル生命科学大学・獣医学研究所(モンゴル)
  • Country Name: MONGOLIA
  • Counterpart Institution: モンゴル生命科学大学・獣医学研究所
• [Int'l Joint Research] 国立獣医学研究所(スリランカ)
  • Country Name: SRI LANKA
  • Counterpart Institution: 国立獣医学研究所
• [Int'l Joint Research] University of Rajshahi(バングラデシュ)
  • Country Name: BANGLADESH
  • Counterpart Institution: University of Rajshahi
• [Int'l Joint Research] フエ大学(ベトナム)
  • Country Name: VIET NAM
  • Counterpart Institution: フエ大学
• [Int'l Joint Research] Makerere大学(ウガンダ)
  • Country Name: UGANDA
  • Counterpart Institution: Makerere大学
• [Int'l Joint Research]
  • # of Other Countries: 3
• [Journal Article] Molecular epidemiological survey of Babesia bovis, Babesia bigemina, and Babesia sp. Mymensingh infections in Mongolian cattle (2020)
  • Author(s): Otgonsuren Davaajav、Sivakumar Thillaiampalam、Yokoyama Naoaki et al.
  • Journal Title: Parasitology International Volume: 77 Pages: 102107～102107
  • DOI: 10.1016/j.parint.2020.102107
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Host range and geographical distribution of Babesia sp. Mymensingh (2020)
  • Author(s): Sivakumar Thillaiampalam、Tuvshintulga Bumduuren、Kothalawala Hemal、Silva Seekkuge Susil Priyantha、Lan Dinh Thi Bich、Long Phung Thang、Yba?ez Adrian Patalinghug、Yba?ez Rochelle Haidee Daclan、Francisco Benitez Daniel、Tayebwa Dickson Stuart、DE Macedo Alan Caine Costa、Schnittger Leonhard、Yokoyama Naoaki
  • Journal Title: Transboundary and Emerging Diseases Volume: - Pages: -
  • DOI: 10.1111/tbed.13546
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Discovery of a new Theileria sp. closely related to Theileria annulata in cattle from Sri Lanka (2019)
  • Author(s): Sivakumar Thillaiampalam、Fujita Shiori、Tuvshintulga Bumduuren、Kothalawala Hemal、Silva Seekkuge Susil Priyantha、Yokoyama Naoaki
  • Journal Title: Scientific Reports Volume: 9 Pages: -
  • DOI: 10.1038/s41598-019-52512-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] First Molecular detection of <i>Theileria annulata</i> in Bangladesh (2019)
  • Author(s): MONI Mst. Ishrat Zerin、HAYASHI Kei、SIVAKUMAR Thillaiapalam、RAHMAN Moizur、NAHAR Lovely、ISLAM Md. Zakirul、YOKOYAMA Naoaki、KITOH Katsuya、APPIAH-KWARTENG Cornelia、TAKASHIMA Yasuhiro
  • Journal Title: Journal of Veterinary Medical Science Volume: 81 Pages: 1197～1200
  • DOI: 10.1292/jvms.19-0220
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Epidemiological survey of hemoprotozoan parasites in cattle from low-country wet zone in Sri Lanka (2019)
  • Author(s): Gunasekara Erandi、Sivakumar Thillaiampalam、Kothalawala Hemal、Abeysekera Thuduwege Sanath、Weerasingha Amitha Sampath、Vimalakumar Singarayar Caniciyas、Kanagaratnam Ratnam、Yapa Palitha Rohana、Zhyldyz Atambekova、Igarashi Ikuo、Silva Seekkuge Susil Priyantha、Yokoyama Naoaki
  • Journal Title: Parasitology International Volume: 71 Pages: 5～10
  • DOI: 10.1016/j.parint.2019.03.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serosurvey of Babesia bovis and Babesia bigemina in cattle in Mongolia (2018)
  • Author(s): Battsetseg Badgar、Sivakumar Thillaiampalam、Naranbaatar Khandsuren、Narantsatsral Sandagdorj、Myagmarsuren Punsantsogvoo、Enkhtaivan Batsaikhan、Davaasuren Batdorj、Mizushima Daiki、Weerasooriya Gayani、Igarashi Ikuo、Battur Banzragch、Yokoyama Naoaki
  • Journal Title: Veterinary Parasitology: Regional Studies and Reports Volume: 13 Pages: 85～91
  • DOI: 10.1016/j.vprsr.2018.04.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genetic Analysis of Babesia Isolates from Cattle with Clinical Babesiosis in Sri Lanka (2018)
  • Author(s): Sivakumar Thillaiampalam、Tuvshintulga Bumduuren、Zhyldyz Atambekova、Kothalawala Hemal、Yapa Palitha Rohana、Kanagaratnam Ratnam、Vimalakumar Singarayar Caniciyas、Abeysekera Thuduwege Sanath、Weerasingha Amitha Sampath、Yamagishi Junya、Igarashi Ikuo、Silva Seekkuge Susil Priyantha、Yokoyama Naoaki
  • Journal Title: Journal of Clinical Microbiology Volume: 56 Pages: -
  • DOI: 10.1128/JCM.00895-18
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular epidemiology of Babesia species, Theileria parva, and Anaplasma marginale infecting cattle and the tick control malpractices in Central and Eastern Uganda (2018)
  • Author(s): Tayebwa Dickson Stuart、Sivakumar Thillaiampalam、Yokoyama Naoaki、Igarashi Ikuo et al.
  • Journal Title: Ticks and Tick-borne Diseases Volume: 9 Pages: 1475～1483
  • DOI: 10.1016/j.ttbdis.2018.06.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Transovarial persistence of Babesia ovata DNA in a hard tick, Haemaphysalis longicornis, in a semi-artificial mouse skin membrane feeding system (2018)
  • Author(s): Umemiya-Shirafuji Rika、Hatta Takeshi、Okubo Kazuhiro、Sato Moeko、Maeda Hiroki、Kume Aiko、Yokoyama Naoaki、Igarashi Ikuo、Tsuji Naotoshi、Fujisaki Kozo、Inoue Noboru、Suzuki Hiroshi
  • Journal Title: Acta Parasitologica Volume: 63 Pages: 433～433
  • DOI: 10.1515/ap-2018-0051
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serological and molecular surveys of Babesia bovis and Babesia bigemina among native cattle and cattle imported from Thailand in Hue, Vietnam (2018)
  • Author(s): SIVAKUMAR Thillaiampalam、LAN Dinh Thi Bich、LONG Phung Thang、VIET Le Quoc、WEERASOORIYA Gayani、KUME Aiko、SUGANUMA Keisuke、IGARASHI Ikuo、YOKOYAMA Naoaki
  • Journal Title: Journal of Veterinary Medical Science Volume: 80 Pages: 333～336
  • DOI: 10.1292/jvms.17-0549
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Expressing of Green Fluorescent Protein in intraerythrocytic stage of Theileria equi (2019)
  • Author(s): Arifin Nugraha，Bumduuren Tuvshintulga，Ming Ming Liu，Xuenan Xuan，Naoaki Yokoyama，Ikuo Igarashi
  • Organizer: 第60回熱帯医学会大会
• [Presentation] Host range and distribution of Babesia sp. Mymensingh (2019)
  • Author(s): Yokoyama, N.、Sivakumar, T.
  • Organizer: 第162回日本獣医学会学術集会
• [Presentation] Molecular epidemiology of virulent Babesia parasites in Mongolian cattle (2019)
  • Author(s): Otogonsuren, D., Sivakumar, T., Battur, B., Battsetseg, B., Yokoyama, N.
  • Organizer: 第162回日本獣医学会学術集会
• [Presentation] Discovery of a new Theileria species closely related to Theileria annulata in cattle from Sri Lanka (2019)
  • Author(s): Sivakumar, T.、Yokoyama, N.
  • Organizer: 第162回日本獣医学会学術集会
• [Presentation] Genetic analysis of Babesia isolates from cattle with clinical babesiosis in Sri Lanka (2018)
  • Author(s): Yokoyama, N., Sivakumar, T., Igarashi, I.
  • Organizer: 第59回日本熱帯医学会大会
• [Presentation] Genetic analysis of Babesia isolates in cattle in Sri Lanka (2018)
  • Author(s): Yokoyama, N., Sivakumar, T., Tuvshintulga, B., Igarashi, I.
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] Molecular detection of Babesia bovis in yaks in Mongolia (2018)
  • Author(s): Myagmarsuren, P., Sivakumar, T., Narantsatsral, S., Battur, B., Inoue, N., Yokoyama, N., Battsetseg, B.
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] Mapping the epidemiology of Babesia bovis and Babesia bigemina in cattle in Mongolia (2018)
  • Author(s): Battsetseg, B., Sivakumar, T., Narantsatsral, S., Myagmarsuren, P., Mizutani, D., Igarashi, I., Battur, B., Yokoyama, N.
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] Tools and strategies for the control of bovine piroplasmosis (2018)
  • Author(s): Naoaki Yokoyama
  • Organizer: Sri Lanka Veterinary Association: 70th annual scientific sessions
  • Int'l Joint Research / Invited
• [Remarks] 帯広畜産大学・原虫病研究センター
  • URL: https://www.obihiro.ac.jp/facility/protozoa/