Development of subunit cocktail vaccine against bovine babesiosis

• Project/Area Number: 16H05033
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Obihiro University of Agriculture and Veterinary Medicine
• Principal Investigator: Yokoyama Naoaki 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: ウシバベシア / 牛バベシア病 / ワクチン / 赤血球 / 多型 / マダニ / 牛 / 免疫原性 / オーダーメイド型 / オーダーメイド / サブユニット / 原虫 / バベシア / カクテル / メロゾイト / 侵入阻害試験 / 遺伝子多型 / 赤血球侵入

Outline of Final Research Achievements

The gene polymorphisms of the vaccine candidate antigens of bovine Babesia distributed throughout the world were clarified, and the immunogenicity of each vaccine candidate antigen was confirmed in the infected cattle. In addition, we established an in vitro erythrocyte invasion evaluation system for bovine Babesia, and identified new vaccine candidate antigens. Meanwhile, we discovered a new pathogenic bovine Babesia species and elucidated its global distribution and infected hosts. Furthermore, we succeeded in establishing a tick infection system for bovine Babesia and a production system for transgenic bovine Babesia.

Academic Significance and Societal Importance of the Research Achievements

世界に広く分布するウシバベシアは致死率の高い牛バベシア病の病因となり、その経済的被害の大きさから本原虫病は我が国の家畜法定伝染病に指定されている。しかしながら、いまだ有効なワクチンが開発されていない。本基盤研究による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。今後、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の完成が望まれる。

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)
• [Int'l Joint Research] 国立獣医学研究所(スリランカ)
• [Int'l Joint Research] University of Rajshahi(バングラデシュ)
• [Int'l Joint Research] フエ大学(ベトナム)
• [Int'l Joint Research] Makerere大学(ウガンダ)
• [Int'l Joint Research]
• [Int'l Joint Research] スリランカ獣医学研究所(スリランカ)
• [Int'l Joint Research] モンゴル生命科学大学・獣医学研究所生命科学大学・獣医学研究所(モンゴル)
• [Int'l Joint Research] 獣医学研究所(スリランカ)
• [Int'l Joint Research] フエ大学/フエ農林大学(ベトナム)
• [Int'l Joint Research] 獣医学研究所(モンゴル)
• [Int'l Joint Research] 畜産生産局/カセサート大学(タイ)
• [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、Tuvshintulga Bumduuren、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: 2233-2239
  • 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 Issue: 1
  • DOI: 10.1038/s41598-019-52512-y
  • NAID: 120006769784
  • 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 Issue: 8 Pages: 1197-1200
  • DOI: 10.1292/jvms.19-0220
  • NAID: 130007695235
  • 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
  • NAID: 120006603077
  • 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
  • NAID: 120006684091
  • 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 Issue: 11
  • DOI: 10.1128/jcm.00895-18
  • NAID: 120006540776
  • Peer Reviewed / Open Access / 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、Vudriko Patrick、Tuvshintulga Bumduuren、Guswanto Azirwan、Nugraha Arifin Budiman、Gantuya Sambuu、Batiha Gaber El-Saber、et al.
  • Journal Title: Ticks and Tick-borne Diseases Volume: 9 Issue: 6 Pages: 1475-1483
  • DOI: 10.1016/j.ttbdis.2018.06.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Transovarial persistence ofBabesia ovata DNA in a hard tick, Haemaphysalis longicornis, in a semi-artificialmouse skin membrane feeding system. (2018)
  • Author(s): Umemiya-Shirafuji R, Hatta T, Okubo K, Sato M, Maeda H, Kume A, Yokoyama N,Igarashi I, Tsuji N, Fujisaki K, Inoue N, Suzuki H.
  • Journal Title: Acta Parasitol. Volume: 63 Issue: 2 Pages: 433-433
  • DOI: 10.1515/ap-2018-0051
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serological and molecular surveys of <i>Babesia bovis</i> and <i>Babesia bigemina</i> 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 Issue: 2 Pages: 333-336
  • DOI: 10.1292/jvms.17-0549
  • NAID: 130006410786
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Babesia bovis BOV57, a Theileria parva P67 homolog, is an invasion-related, neutralization-sensitive antigen (2017)
  • Author(s): Ishizaki Takahiro、Sivakumar Thillaiampalam、Hayashida Kyoko、Takemae Hitoshi、Tuvshintulga Bumduuren、Munkhjargal Tserendorj、Guswanto Azirwan、Igarashi Ikuo、Yokoyama Naoaki
  • Journal Title: Infection, Genetics and Evolution Volume: 54 Pages: 138-145
  • DOI: 10.1016/j.meegid.2017.06.025
  • NAID: 120006411414
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Babesia ovata: Taxonomy, phylogeny and epidemiology (Review). (2016)
  • Author(s): Sivakumar, T., Igarashi, I., and Yokoyama, N.
  • Journal Title: Vet. Parasitol. Volume: 229 Pages: 99-106
  • DOI: 10.1016/j.vetpar.2016.10.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Recombinant methionine aminopeptidase protein of Babesia microti: immunobiochemical characterization as a vaccine candidate against human babesiosis. (2016)
  • Author(s): Munkhjargal, T., Yokoyama, N., and Igarashi, I.
  • Journal Title: Parasitol. Res. Volume: 115 Issue: 9 Pages: 3669-76
  • DOI: 10.1007/s00436-016-5172-5
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Epidemiology of bovine hemoprotozoa parasites in cattle and water buffalo in Vietnam (2016)
  • Author(s): Weerasooriya, G., Sivakumar, T., Lan, D.T., Long, P.T., Takemae, H., Igarashi, I., Inoue, N., and Yokoyama, N.
  • Journal Title: Journal of Veterinary Medical Science Volume: 78 Issue: 8 Pages: 1361-1367
  • DOI: 10.1292/jvms.16-0099
  • NAID: 130005261519
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genetic diversity and antigenicity variation of Babesia bovis merozoite surface antigen-1 (MSA-1) in Thailand. (2016)
  • Author(s): Tattiyapong, M., Sivakumar, T., Takemae, H., Simking, P., Jittapalapong, S., Igarashi, I., and Yokoyama, N.
  • Journal Title: Infect. Genet. Evol. Volume: 41 Pages: 255-261
  • DOI: 10.1016/j.meegid.2016.04.021
  • NAID: 120006390947
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification and characterization of profilin antigen among Babesia species as a common vaccine candidate against babesiosis. (2016)
  • Author(s): Munkhjargal, T., Aboge, G.O., Ueno, A., Aboulaila, M., Yokoyama, N., and Igarashi I.
  • Journal Title: Exp. Parasitol. Volume: 166 Pages: 29-36
  • DOI: 10.1016/j.exppara.2016.03.024
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] RBC Invasion and invasion-inhibition assays using free merozoites isolated after cold treatment of Babesia bovis in vitro culture. (2016)
  • Author(s): Ishizaki, T., Sivakumar, T., Hayashida, K., Tuvshintulga, B., Igarashi, I., and Yokoyama N.
  • Journal Title: Exp. Parasitol. Volume: 166 Pages: 10-15
  • DOI: 10.1016/j.exppara.2016.03.010
  • NAID: 120006390946
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Type-specific PCR assays for Babesia bovis msa-1 genotypes in Asia: Revisiting the genetic diversity in Sri Lanka, Mongolia, and Vietnam. (2016)
  • Author(s): Liyanagunawardena N, Sivakumar T, Kothalawala H, Silva SS, Battsetseg B, Lan DT, Inoue N, Igarashi I, Yokoyama N.
  • Journal Title: Infect Genet Evol. Volume: 37 Pages: 64-69
  • DOI: 10.1016/j.meegid.2015.10.029
  • NAID: 120006390924
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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
• [Presentation] Babesia bovis BOV57, a Theileria parva P67 homolog, is an invasion-related, neutralization-sensitive antigen. (2017)
  • Author(s): 石崎隆弘、T. Sivakumar、林田京子、五十嵐郁男、横山直明
  • Organizer: 第160回日本獣医学会学術集会
• [Remarks] 帯広畜産大学・原虫病研究センター
  • URL: https://www.obihiro.ac.jp/facility/protozoa/