Analysis of the life cycle of Babesia in ticks and development of transmission-blocking vaccines

• Project/Area Number: 18H02336
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Obihiro University of Agriculture and Veterinary Medicine
• Principal Investigator: Xuan Xuenan 帯広畜産大学, 原虫病研究センター, 教授 (10292096)
• Co-Investigator(Kenkyū-buntansha): 白藤 梨可 帯広畜産大学, 原虫病研究センター, 准教授 (00549909) ; 正谷 達謄 岐阜大学, 応用生物科学部, 准教授 (70614072) ; 山岸 潤也 北海道大学, 人獣共通感染症国際共同研究所, 准教授 (80535328)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: Babesia gibsoni / マダニ / 媒介機構 / ライフサイクル / 組換えワクチン / バベシア / 生活環 / 有性生殖期誘導 / 有性生殖期マーカー分子 / CCp / 伝播阻止ワクチン / 犬バベシア症 / Babesai gibsoni / Babesia microti / 伝播阻止 / ワクチン / 伝搬阻止

Outline of Final Research Achievements

(1) Whole genome analysis of B. gibsoni: the whole genome of the Japanese isolate NRCPD strain has analyzed, its genome database has been established. (2) construction of GFP-B. gibsoni: Recombinant GFP-expressing B. gibsoni traceable in ticks and dogs were constructed. (3) Induction of sexual stages of B. gibsoni: the sexual stages of B. bisoni was successfully induced by xanthrenic acid . (4) Identification of vaccine candidate molecules: CCp1, CCp2, and CCp3, which are sexual stage-specific expression molecules, were identified from the genome database, and anti-recombinant CCp1, CCp2, and CCp3 antibodies have shown to suppress the growth of sexual stage of B. gibbon.

Academic Significance and Societal Importance of the Research Achievements

犬のバベシア症は世界的に広く認められており、その経済的損失は莫大との試算もあり、臨床獣医学領域において最も重要な感染症のひとつとして取り上げられている。また、一部のバベシア属原虫は人にも感染し、新興人獣共通感染症として近年公衆衛生上注目されている。しかしながら、バベシア症に対する有効なワクチンはいまだに開発されていないのが現状である。そこで、本研究では有性生殖期の虫体を特異的に抑制する組換えワクチン開発の可能性を検討し、将来的にはペット産業に大きな脅威を与えている犬バベシア症の制圧に繋がるものと予想され、学術的な貢献のみならず、大きな社会的貢献にもなるものと期待される。

Research Products

• [Journal Article] Identification of three members of the multidomain adhesion CCp family in Babesia gibsoni (2023)
  • Author(s): Li et al.
  • Journal Title: Acta Trop Volume: 241 Pages: 106890-106890
  • DOI: 10.1016/j.actatropica.2023.106890
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Babesia gibsoni (2022)
  • Author(s): Liu Mingming、Igarashi Ikuo、Xuan Xuenan
  • Journal Title: Trends in Parasitology Volume: 38 Issue: 9 Pages: 815-816
  • DOI: 10.1016/j.pt.2022.03.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Subolesin vaccination inhibits blood feeding and reproduction of Haemaphysalis longicornis in rabbits (2020)
  • Author(s): Lee et al.
  • Journal Title: Parasit Vectors Volume: 13 Issue: 1 Pages: 478-478
  • DOI: 10.1186/s13071-020-04359-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Porin Expression Profiles in Haemaphysalis longicornis Infected With Babesia microti (2020)
  • Author(s): Zheng Weiqing、Umemiya-Shirafuji Rika、Zhang Qian、Okado Kiyoshi、Adjou Moumouni Paul Franck、Suzuki Hiroshi、Chen Haiying、Liu Mingming、Xuan Xuenan
  • Journal Title: Frontiers in Physiology Volume: 11 Pages: 502-502
  • DOI: 10.3389/fphys.2020.00502
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of Haemaphysalis longicornis Genes Differentially Expressed in Response to Babesia microti Infection (2020)
  • Author(s): Zheng Weiqing、Umemiya-Shirafuji Rika、Chen Shengen、Okado Kiyoshi、Adjou Moumouni Paul Franck、Suzuki Hiroshi、Yang Shu、Liu Mingming、Xuan Xuenan
  • Journal Title: Pathogens Volume: 9 Issue: 5 Pages: 378-378
  • DOI: 10.3390/pathogens9050378
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Babesia microti confers macrophage-babed cross-protective immunity against murine malaria (2020)
  • Author(s): Efstratiou et al.
  • Journal Title: Front Cell Infect Microbiol Volume: 10 Pages: 193-193
  • DOI: 10.3389/fcimb.2020.00193
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ransient Transfection of the Zoonotic Parasite Babesia microti (2020)
  • Author(s): Liu M, Ji S, Rizk MA, Adjou Moumouni PF, Galon EM, Li J, Li Y, Zheng W, Benedicto B, Tumwebaze MA, Asada M, Xuan X
  • Journal Title: Pathogens Volume: 9(2) Issue: 2 Pages: 108-108
  • DOI: 10.3390/pathogens9020108
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inhibitory effects of the phytohormone inhibitors fluridone and inabenfide against Babesia gibsoni in vitro (2019)
  • Author(s): Liu et al.
  • Journal Title: Vet Parasitol Volume: 265 Pages: 19-23
  • DOI: 10.1016/j.vetpar.2018.11.018
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Establishment of a stable transfection system for genetic manipulation of Babesia gibsoni (2018)
  • Author(s): Liu Mingming、Adjou Moumouni Paul Franck、Asada Masahito、Hakimi Hassan、Masatani Tatsunori、Vudriko Patrick、Lee Seung-Hun、Kawazu Shin-ichiro、Yamagishi Junya、Xuan Xuenan
  • Journal Title: Parasites & Vectors Volume: 11 Issue: 1 Pages: 260-260
  • DOI: 10.1186/s13071-018-2853-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Genome editing in the human Babesia parasite Babesia microti using the CRISPR-Cas9 system (2019)
  • Author(s): Liu et al.
  • Organizer: 第65回日本寄生虫学会・日本衛生動物学会北日本支部合同大会
• [Presentation] Identification and expression of subolesin in Haemaphysalis longicornis (2019)
  • Author(s): Lee et al.
  • Organizer: 27th Conference of the World Association for the Advancement of Veterinary Parasitology
  • Int'l Joint Research
• [Presentation] Genome editing of Babesia microti using the CRISPR-Cas9 system (2019)
  • Author(s): Liu et al.
  • Organizer: 27th Conference of the World Association for the Advancement of Veterinary Parasitology
  • Int'l Joint Research
• [Presentation] Inhibitory effects of the phytohormone inhibitors fluridone and inabenfide against Babesia gibsoni in vitro (2018)
  • Author(s): Liu et al.
  • Organizer: 第88回日本寄生虫学会
• [Presentation] Establish of a stable transfection system for genetic manipulation of Babesia gibsoni (2018)
  • Author(s): Liu et al.
  • Organizer: 第161回日本獣医学会(招待講演)
  • Invited
• [Presentation] Identification and expression of subolesin in Haemaphysalis longicornis (2018)
  • Author(s): Lee et al.
  • Organizer: 第88回日本寄生虫学会
• [Presentation] Prevalence and molecular characterization of tick-borne pathogens amongst sheep and goats in Sudan (2018)
  • Author(s): Lee et al.
  • Organizer: 14th International Congress of Parasitology
  • Int'l Joint Research