Development of made-to-order type Babesia vaccine

• Project/Area Number: 25660235
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• 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)
• Co-Investigator(Kenkyū-buntansha): INOUE Noboru 帯広畜産大学, 原虫病研究センター, 教授 (10271751)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 原虫 / バベシア / ワクチン / オーダーメイド / 赤血球侵入 / 遺伝子多型 / TRAP-2 / AMA-1 / 牛 / 馬

Outline of Final Research Achievements

In this study, we have isolated erythrocyte invasion-related genes, including those encode MSA, and determined the genetic polymorphism of these genes in Babesia that is distributed in Asia, Africa, and South America. In addition, we revealed the involvement of Babesia vaccine candidate molecules (RAP-1, AMA-1, TRAP) in the parasite’s erythrocyte invasion. Furthermore, in addition to establishing new in vitro tools for the elucidation of the mechanisms associated with erythrocyte invasion as well as for the genetic engineering of Babesia, we clarified the gene expression profiles in the merozoite stage of this parasite. The findings of the present study are useful not only for furthering our understanding of erythrocyte invasion mechanisms of Babesia but also for the development of vaccines against babesiosis.

Research Products

• [Journal Article] The Babesia bovis gene and promoter model: an update from full-length EST analysis. (2014)
  • Author(s): Yamagishi J, Wakaguri H, Yokoyama N, Yamashita R, Suzuki Y, Xuan X, Igarashi I.
  • Journal Title: BMC Genomics Volume: 15 Issue: 1 Pages: 678-678
  • DOI: 10.1186/1471-2164-15-678
  • Peer Reviewed / Open Access
• [Journal Article] PCR detection of Babesia ovata from questing ticks in Japan. (2014)
  • Author(s): Sivakumar T, Tattiyapong M, Okubo K, Suganuma K, Hayashida K, Igarashi I, Zakimi S, Matsumoto K, Inokuma H, Yokoyama N.
  • Journal Title: Ticks Tick Borne Dis. Volume: 5 Issue: 3 Pages: 305-310
  • DOI: 10.1016/j.ttbdis.2013.12.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genetic characterization of Babesia and Theileria parasites in water buffaloes in Sri Lanka. (2014)
  • Author(s): Sivakumar T, Tattiyapong M, Fukushi S, Hayashida K, Kothalawala H, Silva SS, Vimalakumar SC, Kanagaratnam R, Meewewa AS, Suthaharan K, Puvirajan T, de Silva WK, Igarashi I, Yokoyama N.
  • Journal Title: Vet. Parasitol. Volume: 200 Issue: 1-2 Pages: 24-30
  • DOI: 10.1016/j.vetpar.2013.11.029
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Diversity of Babesia bovis merozoite surface antigen genes in the Philippines. (2014)
  • Author(s): Tattiyapong M, Sivakumar T, Ybanez AP, Ybanez RH, Perez ZO, Guswanto A, Igarashi I, Yokoyama N.
  • Journal Title: Parasitol. Int. Volume: 63 Issue: 1 Pages: 57-63
  • DOI: 10.1016/j.parint.2013.09.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Babesia ovata in cattle: A review. (2013)
  • Author(s): Sivakumar, T., and Yokoyama, N.
  • Journal Title: Jpn. J. Vet. Parasitol. Volume: 12 Pages: 11-20
  • Peer Reviewed
• [Journal Article] A PCR Based Survey of <i>Babesia ovata</i> in Cattle from Various Asian, African and South American Countries (2013)
  • Author(s): Yoshinari, T., Sivakumar, T., Asada, M., Battsetseg, B., Huang, X., Lan, D. T. B., Inpankaew, T., Ybanez, A. P., Alhassan, A., Thekisoe, O. M. M., de macido, A. C., Inokuma, H., Igarashi, I., and Yokoyama, N
  • Journal Title: Journal of Veterinary Medical Science Volume: 75 Issue: 2 Pages: 211-214
  • DOI: 10.1292/jvms.12-0329
  • NAID: 130001879670
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] Prevalence and genetic diversity of equine piroplasms in Tov province, Mongolia. (2013)
  • Author(s): Munkhjargal T, Sivakumar T, Battsetseg B, Nyamjargal T, Aboulaila M, et al.
  • Journal Title: Infection, Genetics and Evolution Volume: 16 Pages: 178-185
  • DOI: 10.1016/j.meegid.2013.02.005
  • Peer Reviewed
• [Journal Article] Molecular survey of bovine vector-borne pathogens in Cebu (2013)
  • Author(s): Ybanez, A.P., Sivakumar, T., Ybanez, R.H., Vincoy, M.R., Tingson, J.A., Perez, Z.O., Gabotero, S.R., Buchorno, L.P., Inoue, N., Matsumoto, K., Inokuma, H., and Yokoyama, N
  • Journal Title: Philippines. Vet. Parasitol Volume: 196 Issue: 1-2 Pages: 13-20
  • DOI: 10.1016/j.vetpar.2013.02.013
  • Peer Reviewed
• [Journal Article] Genetic diversity of merozoite surface antigens in Babesia bovis detected from Sri Lankan cattle (2013)
  • Author(s): Sivakumar, T., Okubo, K., Igarashi, I., de Silva, W.K., Kothalawala, H., Silva, S.S., Vimalakumar, S.C., Meewewa, A.S., and Yokoyama, N
  • Journal Title: Infect. Genet. Evol Volume: 19 Pages: 134-40
  • DOI: 10.1016/j.meegid.2013.07.001
  • Peer Reviewed
• [Journal Article] The Genetic Diversity of Merozoite Surface Antigen 1 (MSA-1) among <i>Babesia bovis</i> Detected from Cattle Populations in Thailand, Brazil and Ghana (2013)
  • Author(s): Nagano, D., Sivakumar, T., de DE Macedo, A.C., Inpankaew, T., Alhassan, A., Igarashi, I., and Yokoyama, N
  • Journal Title: Journal of Veterinary Medical Science Volume: 75 Issue: 11 Pages: 1463-1470
  • DOI: 10.1292/jvms.13-0251
  • NAID: 130003362252
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] PCR Detection and Genetic Diversity of Bovine Hemoprotozoan Parasites in Vietnam (2013)
  • Author(s): Sivakumar, T., Lan, D.T., Long, P.T., Yoshinari, T., Tattiyapong, M., Guswanto, A., Okubo, K., Igarashi, I., Inoue, N., Xuan, X., and Yokoyama, N
  • Journal Title: Journal of Veterinary Medical Science Volume: 75 Issue: 11 Pages: 1455-1462
  • DOI: 10.1292/jvms.13-0221
  • NAID: 130003362251
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] The molecular prevalence and MSA-2b gene-based genetic diversity of Babesia bovis in dairy cattle in Thailand (2013)
  • Author(s): Simking, P., Saengow, S., Bangphoomi, K., Sarataphan, N., Wongnarkpet, S., Inpankaew, T., Jittapalapong, S., Munkhjargal, T., Sivakumar, T., Yokoyama, N., and Igarashi, I
  • Journal Title: Vet. Parasitol Volume: 197 Issue: 3-4 Pages: 642-8
  • DOI: 10.1016/j.vetpar.2013.07.015
  • Peer Reviewed
• [Journal Article] Molecular Characterization of a New Babesia bovis Thrombospondin-Related Anonymous Protein (BbTRAP2) (2013)
  • Author(s): Terkawi, M.A., Ratthanophart, J., Salama, A., Aboulaila, M., Asada, M., Ueno, A., Alhasan, H., Guswanto, A., Masatani, T., Yokoyama, N., Nishikawa, Y., Xuan, X., and Igarashi, I
  • Journal Title: PLoS One Volume: 8 Issue: 12 Pages: e83305-e83305
  • DOI: 10.1371/journal.pone.0083305
  • Peer Reviewed
• [Journal Article] Specific antibody to a conserved region of Babesia apical membrane antigen-1 inhibited the invasion of B. bovis into the erythrocyte (2013)
  • Author(s): Salama, A. A., Terkawi, M. A., Kawai, S., AbouLaila, M., Nayel, M., Mousa, A., Zaghawa, A., Yokoyama, N., and Igarashi, I
  • Journal Title: Exp Parasitol Volume: 135 Issue: 3 Pages: 623-8
  • DOI: 10.1016/j.exppara.2013.09.017
  • Peer Reviewed
• [Presentation] Genetic variations in merozoite surface antigen genes of Babesia bovis detected in Vietnamese cattle and water buffaloes. (2015)
  • Author(s): 横山直明、Sivakumar Thillaiampalam、五十嵐郁男、井上昇
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学（東京）
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Genetic diversity of Babesia bovis merozoite surface antigen genes: Implications for strain verification and immune control. (2015)
  • Author(s): Sivakumar Thillaiampalam、横山直明
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学（東京）
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] WR99210選択システム及びブラスチシジンS選択システムの併用によるBabesia bovis遺伝子改変技術の確立及びノックアウト遺伝子相補実験への応用 (2015)
  • Author(s): 麻田正仁、八幡一英、Hakimi Hassan、横山直明、五十嵐郁男、金子修、Suares Carlos、河津信一郎
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学（東京）
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] On ice法を用いた赤血球侵入能を有する赤血球外バベシアの精製 (2014)
  • Author(s): 石崎隆弘、Sivakumar Thillaiamampalam、五十嵐郁男、横山直明
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 北海道大学（札幌）
  • Year and Date: 2014-09-09 – 2014-09-12
• [Presentation] Babesia bovisにおけるダブルトランスフェクション法の確立 (2014)
  • Author(s): 麻田正仁、Carlos Suares、Hassan Hakimi、横山直明、五十嵐郁男、八幡一英、金子修、河津信一郎
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 北海道大学（札幌）
  • Year and Date: 2014-09-09 – 2014-09-12
• [Presentation] Babesia ovata: Epidemiology and clinical significance. (2014)
  • Author(s): 横山直明、Sivakumar, T., 五十嵐郁男、猪熊 壽
  • Organizer: 第83回日本寄生虫学会
  • Place of Presentation: 愛媛大学
• [Presentation] Epidemiology of Babesia and Theirelia parasites in cattle and water buffalo populations in Sri Lanka. (2014)
  • Author(s): Sivakumar, T., 林田京子、五十嵐郁男、横山直明
  • Organizer: 第83回日本寄生虫学会
  • Place of Presentation: 愛媛大学